==================================BSR13================================== 13. Papers which examine the effect of opiates (not limited to morphine) on the synthesis or release of serotonin (5-hydroxytryptamine) or norepinephrine. Also, the effect of norepinephrine systems on the influence of opiates on the serotonin system. 1 UI - 87066396 AU - Han JS ; Ding XZ ; Fan SG TI - Cholecystokinin octapeptide (CCK-8): antagonism to electroacupuncture analgesia and a possible role in electroacupuncture tolerance. AB - The analgesic effect produced by electroacupuncture (EA) stimulation in the rat was dose-dependently antagonized by cholecystokinin octapeptide (CCK-8) administered intracerebroventricularly (i.c.v.) or intrathecally (i.th) at a dose range of 0.25-4 ng. This effect had an immediate onset and lasted for at least 4 h. CCK-8 per se, however, did not affect baseline tail flick latency. Rats subjected to prolonged EA stimulation developed EA tolerance as well as cross-tolerance to morphine. These tolerances could be postponed or reversed by i.c.v. or i.th injection of antiserum against CCK-8. While CCK-8 antagonized opioid analgesia, it did not affect analgesia induced by 5-hydroxytryptamine (5-HT) or norepinephrine (NE). Moreover, CCK-8 antiserum did not alter the basic level of nociception, nor did it potentiate EA analgesia in naive rats. It is concluded that prolonged EA stimulation results in a profound release of opioids which may trigger the release of CCK-8 in the central nervous system to counteract the opioid component of EA analgesia. This mechanism may account, at least in part, for the development of EA tolerance. MH - *Acupuncture ; Animal ; *Electroanalgesia/METHODS ; *Electrotherapy/ METHODS ; Female ; Immune Sera/ADMINISTRATION & DOSAGE/PHARMACODYNAMICS ; Injections, Spinal ; Male ; Morphine/PHARMACODYNAMICS ; Norepinephrine/ PHARMACODYNAMICS ; Pain/*PHYSIOPATHOLOGY/THERAPY ; Rats ; Regression Analysis ; Serotonin/PHARMACODYNAMICS ; Sincalide/ADMINISTRATION & DOSAGE/ *PHARMACODYNAMICS ; Support, Non-U.S. Gov't ; Time Factors SO - Pain 1986 Oct;27(1):101-15 2 UI - 87065481 AU - Petersen SL ; Barraclough CA TI - Effect of naloxone and morphine on LH and prolactin release in androgen-sterilized rats. AB - Many studies suggest that the hypothalamic opiate system modulates the secretion of LH and prolactin (PRL) by its effects on catecholamine release. We previously provided evidence that the LH response to the opiate receptor antagonist naloxone (NAL) may depend upon spontaneous activity in the hypothalamic noradrenergic system at the time the drug is administered. Thus, when NAL is given to rats which have low turnovers of hypothalamic norepinephrine (NE), only small transient rises in LH occur. This is contrasted to the effects of NAL on the LH responses of animals with high rates of NE turnover where marked amplification of phasic LH release is observed. In the present studies, we examined the effects of NAL on LH and morphine on PRL responses in androgen-sterilized rats (ASR). These animals do not respond to the positive feedback actions of estrogen by having LH surges, and hypothalamic NE turnovers do not increase during the afternoon as they do in normal rats. Female rats were given a single injection of testosterone propionate (50 micrograms s.c.) at 5 days of life and ovariectomized (OVX) at 100 days of age. Seven days later (day 0), estrogen capsules were inserted subcutaneously, and on day 2, their responses to NAL or morphine were examined. Comparable estrogen-treated gonadectomized controls also were studied. In control rats, NAL (10 mg/kg s.c.) markedly amplified the phasic secretion of plasma LH. In contrast, NAL had no effect on the basal afternoon secretion of LH in ASR. To determine if neonatal androgen treatment deleteriously affected opiate-tuberoinfundibular dopamine (TIDA)-serotonergic interactions, a second series of studies was performed.(ABSTRACT TRUNCATED AT 250 WORDS) MH - Animal ; Female ; Hypothalamus/METABOLISM ; Infertility, Female/ETIOLOGY/ METABOLISM ; LH/*SECRETION ; Morphine/*PHARMACODYNAMICS ; Naloxone/ *PHARMACODYNAMICS ; Norepinephrine/METABOLISM ; Pituitary Gland, Anterior/ *SECRETION ; Prolactin/*SECRETION ; Rats ; Rats, Inbred Strains ; Support, U.S. Gov't, P.H.S. ; Testosterone/*PHARMACODYNAMICS SO - Neuroendocrinology 1986;44(1):84-8 3 UI - 87050331 AU - Livett BG ; Marley PD TI - Effects of opioid peptides and morphine on histamine-induced catecholamine secretion from cultured, bovine adrenal chromaffin cells. AB - The effect of opioid peptides and morphine on histamine-induced catecholamine secretion has been studied in monolayer cultures of dispersed, bovine adrenal chromaffin cells. Histamine-induced a dose-dependent secretion of both adrenaline and noradrenaline with a threshold dose of approximately 5 nM, an EC50 of 150 nM and maximal secretion at 10 microM. Catecholamine secretion induced by 1 microM histamine was completely dependent on extracellular calcium, was inhibited in a dose-dependent manner by mepyramine (1 nM-1 microM), and was unaffected by cimetidine (10 microM) and hexamethonium (0.1 mM). Dynorphin-1-13 (1 nM-20 microM), metorphamide (0.1 nM-10 microM), morphine (1 nM-0.1 mM) and diprenorphine (1 nM-0.1 mM) each had no effect on adrenaline or noradrenaline secretion induced by 1 microM histamine. The characteristics of histamine-induced catecholamine secretion from bovine adrenal chromaffin cells were similar to those reported previously for cat and rat adrenal medulla being calcium-dependent and mediated by H1 histamine-receptors. The results with opioid peptides and morphine suggest that endogenous adrenal opioid peptides do not act on the opioid binding sites found on adrenal medullary chromaffin cells to modify their secretory response to histamine. MH - Adrenal Glands/*SECRETION ; Animal ; Calcium/PHYSIOLOGY ; Catecholamines/ *SECRETION ; Cattle ; Cells, Cultured ; Chromaffin System/CYTOLOGY/ *SECRETION ; Endorphins/*PHARMACODYNAMICS ; Epinephrine/SECRETION ; Histamine/*PHARMACODYNAMICS ; Morphine/*PHARMACODYNAMICS ; Norepinephrine/ SECRETION ; Pyrilamine/PHARMACODYNAMICS ; Support, Non-U.S. Gov't SO - Br J Pharmacol 1986 Oct;89(2):327-34 4 UI - 87039411 AU - Schoffelmeer AN ; Putters J ; Mulder AH TI - Activation of presynaptic alpha 2-adrenoceptors attenuates the inhibitory effect of mu-opioid receptor agonists on noradrenaline release from brain slices. AB - 3H-noradrenaline release from rat neocortical slices induced by 15 mM K+ was concentration-dependently inhibited by morphine, [D-Ala2-D-Leu5] enkephalin (DADLE) and the calcium entry blocker Cd2+. Blockade of presynaptic alpha 2-adrenoceptors with phentolamine, almost doubling K+-induced 3H-noradrenaline release, slightly enhanced the relative inhibitory effects of morphine and DADLE, whereas that of Cd2+ remained unaffected. In contrast, activation of presynaptic alpha 2-adrenoceptors with clonidine (1 microM) or TL-99 (1 microM), inhibiting release by about 50%, completely abolished the inhibitory effects of morphine and DADLE without affecting that of Cd2+. When in the presence of 1 microM clonidine adenylate cyclase was activated with forskolin (10 microM), which restored release to the drug-free control level, the opioids still did not display their inhibitory effects. Therefore, mu-opioid receptor efficacy appears to be dependent on the degree of activation of alpha 2-adrenoceptors in central noradrenergic nerve terminals, probably through a local receptor interaction within the nerve terminal membrane. MH - Animal ; Brain Chemistry/*DRUG EFFECTS ; Cadmium/PHARMACODYNAMICS ; Clonidine/PHARMACODYNAMICS ; Enkephalin, Leucine/ANALOGS & DERIVATIVES/ PHARMACODYNAMICS ; Forskolin/PHARMACODYNAMICS ; In Vitro ; Male ; Morphine/PHARMACODYNAMICS ; Norepinephrine/*METABOLISM ; Phentolamine/ PHARMACODYNAMICS ; Rats ; Rats, Inbred Strains ; Receptors, Adrenergic, Alpha/*PHYSIOLOGY ; Receptors, Endorphin/*METABOLISM SO - Naunyn Schmiedebergs Arch Pharmacol 1986 Aug;333(4):377-80 5 UI - 87015891 AU - Chiang CY ; Gao B TI - The modification by systemic morphine of the responses of serotonergic and non-serotonergic neurons in nucleus raphe magnus to heating the tail. AB - In anaesthetised rats, 63 raphe-spinal units in nucleus raphe magnus (NRM) have been identified by means of electrophysiological methods and further classified into serotonergic (5-HT) and non-5-HT units according to their conduction velocity and spontaneous discharge rate. All units, except one, showed either excitatory (n = 39) or inhibitory (n = 23) responses to noxious heating of the tail with hot water at 52 degrees C. The threshold temperature was around 44 degrees C and both types of responses increased with stepwise increases in temperature. The excitatory or inhibitory responses of raphe-spinal units induced by noxious heating of the tail correlated well with those elicited by noxious pinching, but did not correlate with the different transmitter populations (5-HT or non-5-HT) of the NRM unit. The effects of morphine or Fentanyl administration on the heat-induced responses of NRM units was observed. The possible involvement of NRM raphe-spinal units in 'diffuse noxious inhibitory controls' (DNICs) was discussed, particularly in relation to the 'lifting of DNICs' produced by morphine. MH - Animal ; Fentanyl/PHARMACODYNAMICS ; *Heat ; Male ; Morphine/ANTAGONISTS & INHIBITORS/*PHARMACODYNAMICS ; Naloxone/PHARMACODYNAMICS ; Neural Conduction/DRUG EFFECTS ; Neural Transmission ; Neurons/*PHYSIOLOGY ; *Raphe Nuclei ; Rats ; Rats, Inbred Strains ; Serotonin/*METABOLISM ; Tail SO - Pain 1986 Aug;26(2):245-57 6 UI - 87004861 AU - Franklin KB ; Kelly SJ TI - Sympathetic control of tryptophan uptake and morphine analgesia in stressed rats. AB - Guanethidine treatment decreased morphine analgesia exhibited by restrained rats but had no effect on morphine analgesia exhibited by unrestrained rats or on baseline pain sensitivity. Guanethidine also prevented the rise in tryptophan uptake into the brain induced by the restraint stress. It is argued that the prevention of the stress-induced increase in brain tryptophan uptake is causal to guanethidine's attenuation of morphine analgesia exhibited by restrained rats, since the increase in brain tryptophan uptake has already been shown to be critical to this phenomenon. The blockade of the stress-induced increase in brain tryptophan uptake and morphine analgesia by guanethidine support the hypothesis that these effects depend upon sympathetic activity. MH - *Analgesia ; Animal ; Guanethidine/PHARMACODYNAMICS ; Hydroxyindoleacetic Acid/METABOLISM ; Male ; Morphine/*PHARMACODYNAMICS ; Pain/ PHYSIOPATHOLOGY ; Rats ; Restraint, Physical ; Serotonin/METABOLISM ; Stress, Psychological/*PHYSIOPATHOLOGY ; Support, Non-U.S. Gov't ; Sympathetic Nervous System/*PHYSIOLOGY ; Tryptophan/*METABOLISM SO - Eur J Pharmacol 1986 Jul 15;126(1-2):145-50 7 UI - 86313287 AU - Nowakowska E ; Chodera A ; Szczawi:nska K ; Cenajek D TI - Effects of pethidine on central neurotransmitters: changes in the state of tolerance. AB - Cerebral concentrations of neurotransmitters: noradrenaline, dopamine, serotonin and GABA were assayed in male Wistar rats receiving either a single dose of pethidine, or a prolonged treatment with the drug (twice daily for 21 days, im), leading to tolerance development. In tolerant rats the GABA content in the cerebral tissue was increased, and the activity of serotonergic system (assessed from the changes in 5-hydroxyindoleacetic acid level and serotonin turnover rate) was augmented. MH - Animal ; Brain/*METABOLISM ; Dopamine/METABOLISM ; Drug Tolerance ; Hydroxyindoleacetic Acid/METABOLISM ; Male ; Meperidine/*PHARMACODYNAMICS ; Neuroregulators/*METABOLISM ; Norepinephrine/METABOLISM ; Rats ; Rats, Inbred Strains ; Serotonin/METABOLISM SO - Pol J Pharmacol Pharm 1986 Mar-Apr;38(2):143-8 8 UI - 86297335 AU - Bongianni F ; Carla V ; Moroni F ; Pellegrini-Giampietro DE TI - Calcium channel inhibitors suppress the morphine-withdrawal syndrome in rats. AB - The effects of the Ca2+-channel blockers verapamil and nimodipine, on the behavioural signs of naloxone (1 mg kg-1)-induced abstinence syndrome in morphine-dependent rats, were evaluated. The content of noradrenaline (NA) and of its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured, using high performance liquid chromatography and electrochemical detection or gas chromatography-mass spectrometry, in various brain regions of these animals. Possible interactions of nimodipine and verapamil with opioid receptors were evaluated by examining their ability to displace [3H]-naloxone binding to brain membranes. Verapamil (5, 10 and 50 mg kg-1) and nimodipine (1, 5 and 10 mg kg-1) dose-dependently reduced most of the signs of morphine abstinence. Naloxone-precipitated abstinence decreased the NA content in the cortex, hippocampus, brainstem and cerebellum. In the same brain regions the content of MHPG increased, suggesting an increased release of the amine during morphine abstinence. Nimodipine (10 mg kg-1 i.v.) did not change the content of NA or MHPG in the cortex, hippocampus and brainstem. However, nimodipine pre-treatment markedly reduced the changes in NA and MHPG content induced by the abstinence syndrome. Neither verapamil nor nimodipine displaced [3H]-naloxone from its binding sites. These results suggest that Ca2+-channel blockers suppress the behavioural and neurochemical expressions of morphine abstinence by a mechanism that differs from those of opioids or alpha 2-adrenoceptor agonists. MH - Animal ; Behavior, Animal/DRUG EFFECTS ; Brain Chemistry/DRUG EFFECTS ; Calcium Channel Blockers/*PHARMACODYNAMICS ; Methoxyhydroxyphenylglycol/ METABOLISM ; Morphine/*ADVERSE EFFECTS ; Morphine Dependence/METABOLISM ; Naloxone/ANTAGONISTS & INHIBITORS ; Nicotinic Acids/PHARMACODYNAMICS ; Norepinephrine/METABOLISM ; Rats ; Receptors, Endorphin/DRUG EFFECTS ; Substance Withdrawal Syndrome/METABOLISM/*PREVENTION & CONTROL ; Support, Non-U.S. Gov't ; Verapamil/PHARMACODYNAMICS SO - Br J Pharmacol 1986 Jul;88(3):561-7 9 UI - 86287513 AU - Freeman GB ; Nielsen P ; Gibson GE TI - Behavioral and neurochemical correlates of morphine and hypoxia interactions. AB - Decreased oxygen availability (hypoxia) impairs the synthesis of dopamine and serotonin in parallel with a decline in open-field behavior. If hypoxic-induced deficits in dopamine and serotonin metabolism are physiologically important, then stimulation of their synthesis may help reverse hypoxic-induced neurochemical and behavioral deficits. Acute morphine sulfate (50 mg/kg) increased dihydroxyphenylacetic acid/dopamine ratios (DOPAC/DA) (+20%), the conversion of [3H]tyrosine to [3H]dopamine (+73%) and open-field activity (+130%) in CD-1 male mice. However, morphine failed to significantly alter the incorporation of [3H]tryptophan to [3H]serotonin. Morphine antagonized the hypoxic-induced impairment of dopamine metabolism and locomotor activity. DOPAC/DA ratios of hypoxic animals that were treated with morphine were identical to controls, and conversion rates of [3H]tyrosine to [3H]dopamine were increased. Total distance in an automated activity monitor following the combination of morphine and hypoxia increased 79% compared to a 48% decrease with hypoxia alone. These results suggest that both hypoxia and morphine alter the dopaminergic system, but in opposite directions. These interactions may help to explain why morphine is able to ameliorate hypoxic-induced changes in behavior. MH - Animal ; Anoxia/*METABOLISM/PSYCHOLOGY ; Dopamine/*METABOLISM ; Glycolysis ; Male ; Memory ; Mice ; Mice, Inbred Strains ; Morphine/ *PHARMACODYNAMICS ; Motor Activity/*DRUG EFFECTS ; Receptors, Endorphin/ PHYSIOLOGY ; Serotonin/*METABOLISM ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Pharmacol Biochem Behav 1986 Jun;24(6):1687-93 10 UI - 86271100 AU - Pang IH ; Vasko MR TI - Morphine and norepinephrine but not 5-hydroxytryptamine and gamma-aminobutyric acid inhibit the potassium-stimulated release of substance P from rat spinal cord slices. AB - We studied whether morphine, norepinephrine (NE), 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) inhibit the potassium-stimulated release of substance P (SP) from rat spinal cord slices. Male Sprague-Dawley rats were decapitated and a 2-cm segment of lumbosacral spinal cord was removed, chopped into 0.5 X 0.5 mm pieces, weighed, placed in a perfusion chamber and perfused at 37 degrees C with a modified Krebs bicarbonate buffer. Perfusate was collected, lyophilized, then assayed for SP using radioimmunoassay. Exposure of spinal cord tissue to 50 mM KCl for 8 min produced a calcium-dependent increase in the release of SP from a basal level of approximately 0.1 pg/mg tissue/min to 0.3 pg/mg tissue/min. Morphine and NE at concentrations of 10(-4) and 10(-5) M did not alter basal release but caused a significant reduction in the potassium-stimulated release of SP. Naloxone (10(-5) M) and phentolamine (10(-5) M) did not affect SP release but attenuated the effects of morphine and NE, respectively. Naloxone did not antagonize the inhibition of release produced by NE nor did phentolamine block the effect of morphine, suggesting that the actions of the agonists are independent. In contrast, 5-HT and GABA at concentrations of 10(-4) M and 10(-5) M did not significantly alter the basal or potassium-stimulated release of SP. These results demonstrate a differential regulation of SP release in the spinal cord and support the hypothesis that morphine and NE may modify nociception, in part, by inhibiting the release of SP in the spinal cord. MH - Animal ; Comparative Study ; GABA/*PHARMACODYNAMICS ; Male ; Morphine/ *PHARMACODYNAMICS ; Naloxone/PHARMACODYNAMICS ; Norepinephrine/ *PHARMACODYNAMICS ; Phentolamine/PHARMACODYNAMICS ; Potassium/ANTAGONISTS & INHIBITORS ; Rats ; Rats, Inbred Strains ; Serotonin/*PHARMACODYNAMICS ; Spinal Cord/*SECRETION ; Substance P/*SECRETION ; Support, U.S. Gov't, Non-P.H.S. SO - Brain Res 1986 Jun 25;376(2):268-79 11 UI - 86271099 AU - Recio L ; Marin J ; Reviriego J ; Salaices M ; Lopez-Rico M TI - Effect of morphine on the cat middle cerebral artery. AB - Morphine (up to 3 X 10(-4) M) elicited concentration-dependent contractions in cat middle cerebral arteries, higher concentrations induced vasodilation. These responses were annulled in the presence of 1-methyl-3-isobutylxanthine, but unaffected by diphenhydramine, cimetidine, phentolamine or naloxone. Ca2+ suppression blocked the morphine-evoked contractions and Ca2+ addition antagonized its vasodilatory effects. Nifedipine induced a marked relaxation in arteries previously contracted with morphine. Preincubation with nifedipine induced a decrease in the contraction elicited by morphine while it increased the vasodilatory phase. Morphine did not produce a significant effect in femoral arteries. In cerebral arteries previously submitted to an active tone, the opioid-induced vasodilation was unchanged by naloxone, cimetidine, diphenhydramine or ouabain, whereas Ca2+ addition antagonized this effect. These results indicate: that the opioid effects are mediated neither by opiate receptors nor by noradrenaline or histamine release; and that an antagonism exists between Ca2+ and the vasodilation caused by morphine. MH - Adenosine Cyclic Monophosphate/ANALYSIS ; Animal ; Cats ; Cerebral Arteries/ANALYSIS/*DRUG EFFECTS ; Comparative Study ; Femoral Artery/DRUG EFFECTS ; Histamine Liberation/DRUG EFFECTS ; In Vitro ; Morphine/ *PHARMACODYNAMICS ; Naloxone/ANTAGONISTS & INHIBITORS ; Norepinephrine/ SECRETION ; Potassium/ANTAGONISTS & INHIBITORS ; Receptors, Endorphin/ DRUG EFFECTS ; Serotonin Antagonists ; Support, Non-U.S. Gov't SO - Brain Res 1986 Jun 25;376(2):262-7 12 UI - 86255541 AU - Ensinger H ; Hedler L ; Szabo B ; Starke K TI - Bremazocine causes sympatho-inhibition and hypotension in rabbits by activating peripheral kappa-receptors. AB - We have studied the effects of bremazocine on the peripheral sympathetic nervous system and the arterial blood pressure of pithed rabbits with electrically (2 Hz) stimulated sympathetic outflow, and compared them with the effects of Leu-enkephalin and fentanyl. The 3H-noradrenaline plasma clearance and the plasma concentration of noradrenaline were used to calculate the rate of spillover of endogenous noradrenaline into the plasma; the spillover rate reflects the overall release of noradrenaline from postganglionic sympathetic neurones. Bremazocine (10 and 100 micrograms kg-1, followed by an infusion of 2 and 20 micrograms kg-1 h-1, respectively, i.v.) persistently decreased the noradrenaline spillover rate as well as blood pressure. Both effects were antagonized by naloxone. Leu-enkephalin (70 and 350 micrograms kg-1 min-1 i.v.) caused only transient hypotension. Fentanyl decreased blood pressure only at a very high dose (250 micrograms kg-1, followed by an infusion of 500 micrograms kg-1 h-1 i.v.). The effects of Leu-enkephalin and fentanyl were also antagonized by naloxone. When the blood pressure of pithed rabbits was raised by an intravenous infusion of noradrenaline, rather than by electrical stimulation, bremazocine, Leu-enkephalin, and fentanyl failed to produce hypotension. The results indicate that bremazocine inhibits the release of noradrenaline and, in consequence, lowers arterial pressure by activation of peripheral, probably prejunctional, opioid receptors. The receptors appear to be of the kappa-type. MH - Analgesics/*PHARMACODYNAMICS ; Animal ; Benzomorphans/ANTAGONISTS & INHIBITORS/*PHARMACODYNAMICS ; Blood Pressure/*DRUG EFFECTS ; Comparative Study ; Decerebrate State ; Electric Stimulation ; Enkephalin, Leucine/ ANTAGONISTS & INHIBITORS/PHARMACODYNAMICS ; Female ; Fentanyl/ANTAGONISTS & INHIBITORS/PHARMACODYNAMICS ; Male ; Morphinans/*PHARMACODYNAMICS ; Naloxone/PHARMACODYNAMICS ; Norepinephrine/*BLOOD/PHARMACODYNAMICS ; Rabbits ; Receptors, Endorphin/*DRUG EFFECTS ; Support, Non-U.S. Gov't SO - J Cardiovasc Pharmacol 1986 May-Jun;8(3):470-5 13 UI - 86231325 AU - Diez-Guerra FJ ; Augood S ; Emson PC ; Dyer RG TI - Morphine inhibits electrically stimulated noradrenaline release from slices of rat medial preoptic area. AB - Experiments were undertaken to investigate whether the release of noradrenaline (NA) in the preoptic area of female rats is modulated by opiate mechanisms. Slices (300 microns) of preoptic area were incubated individually after loading with 3H-NA and then subjected to electric field stimulation. Morphine (10 microM) significantly reduced the amount of NA released in response to electrical stimulation, an effect that was completely prevented by simultaneous exposure to equimolar naloxone. This inhibitory action of morphine was not dependent upon prior exposure to oestrogen. MH - Animal ; Electric Stimulation ; Estradiol/PHARMACODYNAMICS ; Female ; In Vitro ; Morphine/METABOLISM/*PHARMACODYNAMICS ; Neural Inhibition/*DRUG EFFECTS ; Norepinephrine/*METABOLISM ; Preoptic Area/*DRUG EFFECTS/ METABOLISM ; Rats ; Rats, Inbred Strains ; Support, Non-U.S. Gov't ; Time Factors SO - Neuroendocrinology 1986;43(1):89-91 14 UI - 86217176 AU - Pang IH ; Vasko MR TI - Effect of depletion of spinal cord norepinephrine on morphine-induced antinociception. AB - We studied whether antinociception produced by injection of morphine into the nucleus reticularis paragigantocellularis (NRPG) or by superfusion onto the spinal cord involved norepinephrine (NE)-containing neurons that descend from brainstem into the spinal cord. Spinal cord NE concentrations were depleted with the neurotoxin, 6-hydroxydopamine, and antinociception was measured following morphine injection into NRPG or onto spinal cord. Depletion of cord NE by approximately 90% did not attenuate the antinociceptive effect of either 2 or 10 micrograms of morphine injected intrathecally. In contrast, the depletion did significantly attenuate the antinociceptive effect of 2.5 micrograms morphine injected bilaterally into the NRPG. These results suggest that NE-containing neurons descending from brainstem nuclei into the spinal cord are not important in the analgesia produced by injecting morphine directly onto the spinal cord but may be involved with analgesia produced by morphine injection into the NRPG. MH - Animal ; Efferent Pathways/DRUG EFFECTS ; Injections, Spinal ; Male ; Medulla Oblongata/*DRUG EFFECTS ; Morphine/ADMINISTRATION & DOSAGE/ *PHARMACODYNAMICS ; Norepinephrine/*PHYSIOLOGY ; Pain/DRUG THERAPY ; Rats ; Rats, Inbred Strains ; Reticular Formation/*DRUG EFFECTS ; Serotonin/ PHYSIOLOGY ; Spinal Cord/*DRUG EFFECTS ; Support, U.S. Gov't, Non-P.H.S. SO - Brain Res 1986 Apr 16;371(1):171-6 15 UI - 86108106 AU - Johnston CA ; Negro-Vilar A TI - Maturation of the prolactin and proopiomelanocortin-derived peptide responses to ether stress and morphine: neurochemical analysis. AB - The hormonal and neurochemical responses to acute ether stress, morphine, and/or naloxone were analyzed in infantile (13-day-old) and prepubertal (36-day-old) male CD rats in an attempt to identify a possible neurochemical correlate(s) for the previously demonstrated requisite maturation of the PRL response to ether stress. Neuronal serotonin (5-HT), norepinephrine (NE), and dopamine (DA) activities were examined in the medial preoptic hypothalamic area (MPOH), medial basal hypothalamic area (MBH), and median eminence (ME). Ether stress increased plasma PRL, ACTH, and beta-endorphin-like immunoreactivity (beta end) as well as NE metabolism in the MPOH and MBH and neuronal 5-HT activity in the MBH, and decreased neuronal DA activity in the ME of prepubertal animals. Ether stress elicited similar changes in infantile animals, with the important exceptions that plasma PRL, neuronal 5-HT activity in the MBH, and neuronal DA synthesis in the ME were not affected at this earlier age. Morphine increased plasma PRL, ACTH, and beta end levels, elevated neuronal NE and 5-HT activities in the MPOH and MBH, and decreased DA synthesis in the ME in both infantile and prepubertal animals. Naloxone administration did not alter basal hormone concentrations or neuronal monoamine activity in any brain area, but did prevent all of the morphine-induced changes as well as the ether stress-induced changes in PRL, MBH neuronal 5-HT activity, and DA synthesis in the ME of prepubertal animals. In addition, naloxone augmented the ether stress-induced increases in ACTH and beta end in prepubertal rats. Indirect stimulation of 5-HT neurons by administration of the amino acid precursor of 5-HT, 5-hydroxytryptophan, resulted in decreased DA synthesis in the ME of infantile animals and increased plasma PRL levels in that age group, indicating that this portion of the neurochemical connection is already present in infantile animals. Furthermore, the 5-hydroxytryptophan-induced increase in PRL was blocked by pretreatment with naloxone. The results demonstrate that both the ether stress- and morphine-induced increases in plasma PRL, but not in ACTH or beta end, are associated with increased neuronal 5-HT activity in the MBH and a decreased neuronal DA activity in the ME, that these are opiate receptor-mediated effects, and that infantile rats apparently lack a functional opiate-5-HT connection, which matures some time between days 13 and 36 postnatally. MH - Adrenocorticotropic Hormone/BLOOD ; *Aging ; Animal ; Animals, Newborn/ METABOLISM ; Comparative Study ; Dopamine/METABOLISM ; Endorphins/BLOOD ; Ether, Ethyl ; Hydroxytryptophan/PHARMACODYNAMICS ; Hypothalamus, Middle/ GROWTH & DEVELOPMENT/METABOLISM ; Male ; Median Eminence/GROWTH & DEVELOPMENT/METABOLISM ; Morphine/*PHARMACODYNAMICS ; Neurons/DRUG EFFECTS/METABOLISM ; Norepinephrine/METABOLISM ; Preoptic Area/GROWTH & DEVELOPMENT/METABOLISM ; Pro-Opiomelanocortin/*METABOLISM ; Prolactin/ BLOOD/*METABOLISM ; Rats ; Serotonin/METABOLISM ; Sex Maturation ; Stress/ CHEMICALLY INDUCED/*METABOLISM SO - Endocrinology 1986 Feb;118(2):797-804 16 UI - 86204426 AU - Smith DF TI - The stereoselectivity of serotonin uptake in brain tissue and blood platelets: the topography of the serotonin uptake area. AB - This review concerns effects of stereoisomers on 5-HT uptake in brain tissue and/or blood platelets. All studies in which at least a pair of stereoisomers were used are considered. Differences between effects of stereoisomers of antidepressants as well as other drugs on 5-HT uptake are discussed. The findings indicate that 5-HT uptake is a stereoselective process. A topographical model of the 5-HT uptake area is proposed, based mainly on comparisons between spatial features of stereoisomers that inhibit 5-HT uptake. MH - Alanine/ANALOGS & DERIVATIVES/PHARMACODYNAMICS ; Amphetamine/ PHARMACODYNAMICS ; Aniline Compounds/PHARMACODYNAMICS ; Animal ; Antidepressive Agents/PHARMACODYNAMICS ; Blood Platelets/*METABOLISM ; Brain/*METABOLISM ; Fluoxetin/PHARMACODYNAMICS ; Human ; Male ; Methadone/ PHARMACODYNAMICS ; Mianserin/ANALOGS & DERIVATIVES/PHARMACODYNAMICS ; Morpholines/PHARMACODYNAMICS ; Naphthalenes/PHARMACODYNAMICS ; Nefopam/ PHARMACODYNAMICS ; Nomifensine/PHARMACODYNAMICS ; Piperidines/ PHARMACODYNAMICS ; Rabbits ; Serotonin/*METABOLISM ; Stereoisomers ; Support, Non-U.S. Gov't ; Tranylcypromine/PHARMACODYNAMICS ; Viloxazine/ PHARMACODYNAMICS ; Zimelidine/ANALOGS & DERIVATIVES/PHARMACODYNAMICS SO - Neurosci Biobehav Rev 1986 Spring;10(1):37-46 17 UI - 86203965 AU - Monroe PJ ; Michaux K ; Smith DJ TI - Evaluation of the direct actions of drugs with a serotonergic link in spinal analgesia on the release of [3H]serotonin from spinal cord synaptosomes. AB - Morphine, ketamine, ethylketocyclazocine and quipazine, drugs with an apparent local spinal serotonergic action, which contributes to their analgesic effects, were tested for their ability to alter the release of [3H]serotonin ([3H]5-HT) from a synaptosomal preparation from the spinal cord of the rat. Related compounds including [D-Ala2, D-Leu5]enkephalin (DADLE), n-allylnormetazocine and phencyclidine were also examined. None of the drugs was found to be capable of inducing a direct release of [3H]5-HT or of facilitating potassium-induced release of 5-HT. However, quipazine inhibited the depressant action of exogenous 5-HT on overflow of 3H (mediated through the 5-HT autoreceptor), an action that should facilitate serotonergic neurotransmission. In contrast to the other drugs, DADLE was found to depress K+ stimulated release of 5-HT. The results suggests that the serotonergic mechanism involved in the antinociceptive action of some of these drugs (i.e. ketamine, morphine and ethyl-ketocyclazocine) is not related to direct presynaptic interactions to promote release of 5-HT. On the other hand, a small population of serotonergic nerves critical for analgesia may be involved and are not detected using tissue from the whole spinal cord, However, it seems equally plausible that these drugs may produce their antinociceptive action through interactions with other neurotransmitter systems that in turn interface with the serotonergic nerves, perhaps through interneurons or collateral connections. MH - *Analgesia ; Animal ; Calcium/PHYSIOLOGY ; Cyclazocine/ANALOGS & DERIVATIVES/PHARMACODYNAMICS ; In Vitro ; Ketamine/PHARMACODYNAMICS ; Male ; Morphine/PHARMACODYNAMICS ; Potassium/PHARMACODYNAMICS ; Quipazine/ PHARMACODYNAMICS ; Rats ; Rats, Inbred Strains ; Receptors, Serotonin/ DRUG EFFECTS ; Serotonin/METABOLISM/*PHYSIOLOGY ; Spinal Cord/*METABOLISM ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Synaptosomes/ *METABOLISM SO - Neuropharmacology 1986 Mar;25(3):261-5 18 UI - 86203681 AU - Fuder H ; Buder M ; Riers HD ; Rothacher G TI - On the opioid receptor subtype inhibiting the evoked release of 3H-noradrenaline from guinea-pig atria in vitro. AB - Guinea-pig isolated atria were incubated and loaded with 3H-(-)-noradrenaline. The intrinsic nerves were stimulated with trains of 5 or 35 field pulses (4 Hz), and the evoked efflux of 3H-noradrenaline and of total tritium was determined in the presence of atropine, corticosterone, desipramine, and phentolamine by liquid scintillation spectrometry. Ethylketocyclazocine (1.4 nmol/l, IC50), MR 2033 (9.1 nmol/l), dynorphin A (1-13) (25 nmol/l, peptidase inhibitors present), etorphine (71 nmol/l), and [D-Ala2, D-Leu5]-enkephalin (greater than 10 mumol/l, peptidase inhibitors present) inhibited the stimulation-evoked efflux of 3H-noradrenaline in a concentration-dependent manner, but not morphine up to 10 mumol/l. The inhibition by ethylketocyclazocine, MR 2033, and etorphine was antagonized by naloxone 1 mumol/l. Similarly, the MR 2033 effect was antagonized by SKF 10047 1 mumol/l. All antagonists investigated failed to affect the evoked 3H-noradrenaline efflux when present in the absence of exogenous agonists. Arunlakshana-Schild plots were calculated for the antagonism between ethylketocyclazocine and a pair of stereoisomers, (-)-MR 2266 (20 nmol/l-5 mumol/l) and (+)-MR 2267 (0.3-10 mumol/l) at the presynaptic opioid receptor, and pA2 values were estimated. The isomeric affinity ratio was 60, with pA2 values of (-)-MR 2266, 9.06, and (+)-MR 2267, 7.28, respectively. The results show that the 3H-noradrenaline release can be inhibited via activation of presynaptic opioid receptors. Under the conditions presently investigated endogenous opioids do not modulate the evoked transmitter release. The results favour the idea that a single population (presumably of the kappa-subtype) of opioid receptors is present at guinea-pig atrial noradrenergic nerves. MH - Animal ; Atropine/PHARMACODYNAMICS ; Benzomorphans/PHARMACODYNAMICS ; Binding, Competitive ; Corticosterone/PHARMACODYNAMICS ; Cyclazocine/ ANALOGS & DERIVATIVES/PHARMACODYNAMICS ; Desipramine/PHARMACODYNAMICS ; Dynorphin/PHARMACODYNAMICS ; Enkephalin, Leucine/ANALOGS & DERIVATIVES/ PHARMACODYNAMICS ; Etorphine/PHARMACODYNAMICS ; Guinea Pigs ; Heart Atrium/INNERVATION ; In Vitro ; Morphine/PHARMACODYNAMICS ; Myocardium/ *METABOLISM ; Naloxone/PHARMACODYNAMICS ; Norepinephrine/*METABOLISM ; Peptide Fragments/PHARMACODYNAMICS ; Phentolamine/PHARMACODYNAMICS ; Receptors, Endorphin/*METABOLISM ; Support, Non-U.S. Gov't ; Synapses/ METABOLISM SO - Naunyn Schmiedebergs Arch Pharmacol 1986 Feb;332(2):148-55 19 UI - 86198730 AU - Jackisch R ; Geppert M ; Illes P TI - Characterization of opioid receptors modulating noradrenaline release in the hippocampus of the rabbit. AB - Noradrenaline (NA) release and its modulation via presynaptic opioid receptors were studied in rabbit hippocampal slices, which were preincubated with [3H]NA, continuously superfused in the presence of 30 microM cocaine and stimulated electrically. The evoked release of [3H]NA was strongly reduced by the preferential kappa-agonists ethylketocyclazocine, dynorphin A1-13, dynorphin A, trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] -benzeneacetamide (U-50,488), and (-)-5,9-dimethyl-2'-OH-2-tetrahydrofurfuryl-6,7-benzomorphan [(-)-MR 2034], whereas (+)-MR 2035 [the (+)-enantiomer of (-)-MR 2034] was ineffective. In contrast, the preferential delta-agonists Leu-enkephalin, Met-enkephalin, and D-Ala2-D-Leu5-enkephalin (DADLE) as well as the mu-agonists morphine, normorphine, D-Ala2-Gly-ol5-enkephalin (DAGO), and beta-casomorphin 1-4 amide (morphiceptin) were much less potent. However, in similar experiments on rat hippocampal slices DAGO (1 microM) was much more potent than ethylketocyclazocine (1 microM) or DADLE (1 microM). (-)-N-(3-furylmethyl)-alpha-noretazocine [(-)-MR 2266], 1 microM, a preferential kappa-antagonist, antagonized the effect of ethylketocyclazocine more potently than (-)-naloxone or (+)-MR 2267 [the (+)-enantiomer of (-)-MR 2266]. Given alone, (-)-MR 2266 slightly and (+)-MR 2267 (1 microM each) greatly enhanced NA release, apparently due to alpha 2-adrenoceptor blockade since their effects were completely abolished in the presence of yohimbine (0.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS) MH - Animal ; Benzomorphans/PHARMACODYNAMICS ; Clonidine/PHARMACODYNAMICS ; Cyclazocine/ANALOGS & DERIVATIVES/PHARMACODYNAMICS ; Dynorphin/ PHARMACODYNAMICS ; Endorphins/PHARMACODYNAMICS ; Enkephalin, Leucine/ ANALOGS & DERIVATIVES/PHARMACODYNAMICS ; Enkephalin, Methionine/ PHARMACODYNAMICS ; Enkephalins/PHARMACODYNAMICS ; Hippocampus/*METABOLISM ; Morphine/PHARMACODYNAMICS ; Norepinephrine/*METABOLISM ; Rabbits ; Receptors, Endorphin/*METABOLISM ; Support, Non-U.S. Gov't SO - J Neurochem 1986 Jun;46(6):1802-10 20 UI - 86198719 AU - Schoffelmeer AN ; Wierenga EA ; Mulder AH TI - Role of adenylate cyclase in presynaptic alpha 2-adrenoceptor- and mu-opioid receptor-mediated inhibition of [3H]noradrenaline release from rat brain cortex slices. AB - Rat brain cortex slices, prelabelled with [3H]noradrenaline, were superfused and exposed to electrical biphasic block pulses (1 Hz; 12 mA, 4 ms) or to the Ca2+ ionophore A 23187 (10 microM) in the presence of 1.2 mM Ca2+. Forskolin (10 microM), 8-bromo-cyclic AMP (300 microM), and dibutyryl-cyclic AMP (300 microM) facilitated both the electrically evoked and A 23187-induced [3H]noradrenaline release, whereas the phosphodiesterase inhibitors 3-isobutyl-1-methylxanthine (IBMX, 300 microM) and 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (ZK 62771, 30 microM) enhanced the electrically evoked release only. The inhibitory effects of clonidine (1 nM-1 microM) and the facilitatory effect of phentolamine (0.01-10 microM) on the electrically evoked [3H]noradrenaline release were strongly reduced in the presence of 8-bromo-cyclic AMP. Clonidine (1 microM) reduced and phentolamine (3 microM) enhanced A 23187-induced [3H]noradrenaline release, provided that the slices were simultaneously exposed to forskolin. The inhibitory effects of morphine (1 microM) and [D-Ala2-D-Leu5]enkephalin (DADLE, 0.3 microM), like that of the Ca2+ antagonist Cd2+ (15 microM), on the electrically evoked release of [3H]noradrenaline were not affected by 8-bromo-cyclic AMP. Moreover, morphine and DADLE did not inhibit A 23187-induced release in the absence or presence of forskolin. These data strongly suggest that in contrast to presynaptic mu-opioid receptors, alpha 2-adrenoceptors on noradrenergic nerve terminals are negatively coupled to adenylate cyclase and may thus reduce neurotransmitter release by inhibiting the feed-forward action of cyclic AMP on the secretion process. MH - A-23187/PHARMACODYNAMICS ; Adenosine Cyclic Monophosphate/METABOLISM ; Adenyl Cyclase/*METABOLISM ; Animal ; Cadmium/PHARMACODYNAMICS ; Cerebral Cortex/*ENZYMOLOGY ; Clonidine/PHARMACODYNAMICS ; Dibutyryl Cyclic AMP/ PHARMACODYNAMICS ; Electric Stimulation ; Enkephalin, Leucine/ANALOGS & DERIVATIVES/PHARMACODYNAMICS ; Forskolin/PHARMACODYNAMICS ; Morphine/ PHARMACODYNAMICS ; Norepinephrine/*METABOLISM ; Phentolamine/ PHARMACODYNAMICS ; Pyrrolidinones/PHARMACODYNAMICS ; Rats ; Receptors, Adrenergic, Alpha/*METABOLISM ; Receptors, Endorphin/*METABOLISM ; 1-Methyl-3-Isobutylxanthine/PHARMACODYNAMICS ; 8-Bromo Cyclic Adenosine Monophosphate/PHARMACODYNAMICS SO - J Neurochem 1986 Jun;46(6):1711-7 21 UI - 86171323 AU - Bero LA ; Kuhn CM TI - Catecholaminergic regulation of opiate-stimulated growth hormone secretion in the developing rat. AB - In adult rats, the noradrenergic system plays a role in pulsatile and opiate-stimulated growth hormone (GH) secretion through stimulation of alpha-2 adrenergic receptors. The present studies examine catecholaminergic mechanisms which might regulate GH release in the neonatal rat. Catecholaminergic involvement in opiate-induced GH secretion was examined in 10-day-old and 30-day-old rats. Rats were sacrificed 30 min after administration of methadone (2.5 mg/kg s.c.) and serum was analyzed for GH by radioimmunoassay. Reserpine (1 mg/kg s.c.) abolished methadone-induced GH release in neonatal rats. Haloperidol (1 mg/kg s.c.) but not cyproheptadine (5 mg/kg i.p.) attenuated methadone-stimulated GH release. The role of noradrenergic neurons in opiate-induced GH secretion was examined by pretreating rats with diethyldithiocarbamate (400 mg/kg i.p.) or phenoxybenzamine (10 mg/kg i.p.). Both treatments blocked methadone-induced GH release in neonatal rats. In 30-day-old rats, pretreatment with yohimbine (2.5 mg/kg i.p.), but not prazosin (2.5 mg/kg s.c.) blocked opiate-induced GH release. Although selective blockade by these alpha-1 and alpha-2 antagonists could not be demonstrated in neonatal rats, the alpha-2 agonist, clonidine, did stimulate GH release in a dose-related manner. Findings suggest that noradrenergic mechanisms participate in the regulation of GH secretion in both neonatal and adult rats. A tonically active alpha-2 system is demonstrable in neonates despite the absence of GH surges. The GH response to opiates appears to be mediated through this mechanism. Neural regulation of surging may develop as a separate pathway or become superimposed on the neonatal circuit. MH - Animal ; Catecholamines/*PHYSIOLOGY ; Cyproheptadine/PHARMACODYNAMICS ; Dopamine/PHYSIOLOGY ; Haloperidol/PHARMACODYNAMICS ; Methadone/ *PHARMACODYNAMICS ; Norepinephrine/PHYSIOLOGY ; Rats ; Receptors, Adrenergic, Alpha/*PHYSIOLOGY ; Reserpine/PHARMACODYNAMICS ; Serotonin/ PHYSIOLOGY ; Somatotropin/*SECRETION ; Support, U.S. Gov't, P.H.S. ; Sympatholytics/PHARMACODYNAMICS SO - J Pharmacol Exp Ther 1986 Apr;237(1):137-42 22 UI - 86156857 AU - Samuelson PN ; Reves JG ; Kirklin JK ; Bradley E Jr ; Wilson KD ; Adams M TI - Comparison of sufentanil and enflurane-nitrous oxide anesthesia for myocardial revascularization. AB - This study compared the stress response in patients with coronary artery disease undergoing myocardial revascularization anesthetized with either sufentanil and oxygen or enflurane-nitrous oxide and oxygen. Throughout induction and maintenance of anesthesia, and while the patients were in the intensive care unit, hemodynamics plus plasma catecholamine, sufentanil, and enflurane concentrations were recorded and compared. Three groups were studied: sufentanil, 15 micrograms/kg at induction; sufentanil, 15 micrograms/kg at induction plus 10 micrograms/kg on initiation of cardiopulmonary bypass (CPB); and enflurane anesthesia. Hemodynamics were remarkably stable in all groups but required considerable fine tuning when enflurane was administered. The "stress: of CPB was blunted by the additional dose of sufentanil, as well as by enflurane. This was reflected in those patients receiving the extra sufentanil or enflurane by less severe increases in their epinephrine or norepinephrine concentrations and by less frequent use of sodium nitroprusside to control mean arterial pressure compared to the group of patients given the lower-dose sufentanil. This study suggests that higher blood levels of sufentanil can attenuate, but not eliminate, the stress response to CPB, as can enflurane, and that both the narcotic and inhalation anesthetic techniques for patients with coronary artery disease were quite satisfactory. MH - *Anesthesia ; Cardiopulmonary Bypass ; Comparative Study ; Creatine Kinase/BLOOD ; *Enflurane/PHARMACODYNAMICS ; Epinephrine/BLOOD ; Female ; Fentanyl/*ANALOGS & DERIVATIVES/BLOOD/PHARMACODYNAMICS ; Hemodynamics/ DRUG EFFECTS ; Human ; Intensive Care Units ; Male ; Middle Age ; *Myocardial Revascularization ; Nitroprusside/PHARMACODYNAMICS ; *Nitrous Oxide/PHARMACODYNAMICS ; Norepinephrine/BLOOD SO - Anesth Analg 1986 Mar;65(3):217-26 23 UI - 86105241 AU - Akabori A ; Barraclough CA TI - Effects of morphine on luteinizing hormone secretion and catecholamine turnover in the hypothalamus of estrogen-treated rats. AB - This study examined the effects of morphine sulfate and naloxone alone or in combination on phasic luteinizing hormone (LH) secretion in estrogen-treated ovariectomized rats. Thereafter, the effects of morphine on initial concentrations, rate constants and rates of turnovers of norepinephrine and dopamine were evaluated in untreated or morphine-injected, estrogen-primed rats. Morphine, when given at 12.30 h, completely suppressed the spontaneous LH surges which occur in steroid-treated rats. The opiate antagonist, naloxone, (12.15 h) markedly amplified and advanced the time of LH release and combination of morphine and naloxone produced peak afternoon LH values which were intermediate between those obtained in controls and in rats receiving only naloxone. Norepinephrine (NE) and dopamine (DA) turnover were calculated from data obtained in groups of rats sacrificed 0.45 or 90 min after administering 300 mg/kg b. wt. i.p. of alpha-methyl-p-tyrosine (alpha-MPT) at 10.00 or 15.00 h. In these experiments, the medial preoptic nucleus (MPN) and the median eminence (ME) were microdissected and analyzed for changes in NE and DA concentrations by a radioenzymatic procedure. In estrogen-treated rats, NE rate constants and turnover significantly increased at 15.00 vs 10.00 h in MPN and ME concomitant with increases in serum LH. Morphine blocked both increases in rate constants and turnover in the MPN and ME and also significantly reduced initial concentrations of NE in the MPN. None of the DA parameters measured in MPN or ME changed in estrogen-treated controls between morning and afternoon. Further, while morphine did not affect DA turnover in the MPN, DA turnover declined in the ME.(ABSTRACT TRUNCATED AT 250 WORDS) MH - Animal ; Dopamine/*METABOLISM ; Estradiol/*PHARMACODYNAMICS ; Hypothalamus/*METABOLISM ; LH/*SECRETION ; Median Eminence/METABOLISM ; Morphine/*PHARMACODYNAMICS ; Naloxone/PHARMACODYNAMICS ; Norepinephrine/ *METABOLISM ; Preoptic Area/METABOLISM ; Rats ; Rats, Inbred Strains ; Support, U.S. Gov't, P.H.S. SO - Brain Res 1986 Jan 8;362(2):221-6