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M A Mayfield

Publications and source records attributed to M A Mayfield.

13 recordsLinked to original sources
PubMed1986

Opioid kappa receptors and the secretion of prolactin (PRL) and growth hormone (GH) in the rat. I. Effects of opioid kappa receptor agonists bremazocine and U-50,488 on secretion of PRL and GH: comparison with morphine.

The effects of bremazocine and U-50,488, two selective opioid kappa receptor agonists, and the preferential mu receptor agonist morphine on the secretion of PRL and GH were compared in conscious male rats bearing permanent right atrial cannulae for serial blood sampling and drug delivery. All three opioids stimulated PRL secretion in a dose-related manner, but the kappa agonists differed from morphine in several respects. They were considerably more potent than morphine in triggering a PRL response, but were unable to elevate PRL levels to more than 100 ng/ml, whereas morphine, at the highest dose (4.5 mg/kg), induced an almost twice larger response. Also their PRL-releasing effect was inhibited more strongly by the preferential kappa receptor antagonist Mr-2266 than by naloxone, whereas Mr-2266 and naloxone, which are equipotent as antagonists of the mu receptors, were equipotent in suppressing the PRL-stimulating effect of morphine, a mu agonist. In a complete contrast to morphine, which effectively stimulated GH secretion, the kappa agonists had no effect on GH release at lower doses and suppressed it at higher doses. It is concluded that the PRL-releasing effect of the kappa agonists is mediated by the kappa receptors which may participate with the mu receptors in regulation of PRL secretion by opioids. The GH-inhibiting effect of the kappa agonists requires further clarification.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1986

Opioid kappa receptors and the secretion of prolactin (PRL) and growth hormone (GH) in the rat. II. GH and PRL release-inhibiting effects of the opioid kappa receptor agonists bremazocine and U-50,488.

An analysis of the GH release-inhibiting action of the opioid kappa receptor agonists bremazocine and U-50,488, established earlier, was attempted by testing the agonists against activation of GH secretion by morphine or clonidine in male rats bearing right atrial cannulae for serial blood sampling and drug delivery. Both kappa agonists inhibited the effect of subsequent administration of clonidine in a dose-related manner. Bremazocine was approximately ten times more potent than U-50,488, a ratio corresponding to the known affinities of the two compounds for the kappa receptors. The inhibiting action of bremazocine was more strongly reversed by the preferential kappa receptor antagonist Mr-2266 than by naloxone, neither of which interfered with the GH-stimulating effect of clonidine. Bremazocine, however, did not alter the activation of GH secretion by exogenous growth hormone releasing factor. Thus, the inhibiting effect of bremazocine and probably U-50,488 seems to be derived from stimulation of the kappa receptors which in turn activates a GH release inhibiting mechanism of unknown identify which, however, does not involve release of somatostatin. Both kappa agonists also inhibited the effect of morphine, but in this case U-50,488 was approximately hundred times less effective than bremazocine. Since bremazocine and U-50,488 are antagonists of the delta receptors, which seem to mediate the GH-releasing effect to morphine, their inhibiting effect in this instance may be related to this property rather than to an action on the kappa receptors. Bremazocine, but not U-50,488, was also highly effective in inhibiting stimulation of PRL secretion by morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1984

Differential role of the opioid mu and delta receptors in the activation of prolactin (PRL) and growth hormone (GH) secretion by morphine in the male rat.

Administration of naloxazone (50 mg/kg i.v.), an irreversible, selective and long acting antagonist of the mu 1 subclass of the opioid receptors, strongly reduced stimulation of PRL secretion by morphine (5.0 mg/kg i.v.) injected 24 hours later into conscious, unrestrained rats. In contrast, the effect of morphine on PRL release was unimpaired in rats treated 24 hours beforehand with either the reversible opioid antagonist naloxone (50 mg/kg i.v.), or the vehicle for naloxazone. A complete suppression of the PRL response to morphine (3.0 mg/kg i.v.) was observed in animals given intraventricular (IVT) injection of beta- funaltrexamine (beta-FNA, 2.5 micrograms), another selective, irreversible and long acting antagonist of the mu receptors, 24 hours beforehand. Neither naloxazone nor beta-FNA had any effect on the activation of GH secretion by morphine, which, however, was conspicuously reduced by ICI 154, 129, a preferential delta receptor antagonist, injected IVT (50 micrograms) 5 minutes before morphine. ICI 154, 129 had no effect on the PRL response to morphine. It is concluded that the PRL stimulating effect of morphine is mediated by the mu receptors, whereas activation of GH probably involves the delta sites.

Animals↗
PubMed1982

On the prolactin-inhibiting effect of neurotensin. The role of dopamine.

Neurotensin (NT) when injected in a dose of 5 micrograms into the third cerebral ventricle of conscious, unrestrained male rats, outfitted with chronic third ventricle and jugular cannulae, decreased the resting prolactin (PRL) levels. NT (5 micrograms) also markedly inhibited the PRL-releasing effect of activation of central serotonin receptors by 5-hydroxytryptophan (5HTP, 15 mg/kg) in animals pretreated with fluoxetine (4 mg/kg). however, interruption of dopamine (DA) neurotransmission by either alpha-methyl-p-tyrosine (alpha MT, 250 mg/kg) or spiroperidol (0.3 mg/kg) led to a blockade of the PRL-inhibiting effect of NT. Treatment of animal with alpha MT prior to the injection of fluoxetine and 5HTP also blocked the PRL-inhibiting effect of NT. These results suggest that the central dopaminergic system mediates the PRL-inhibitory effect of NT.

Animals↗
PubMed1981

On the mode of the prolactin release-inhibiting action of the serotonin receptor blockers metergoline, methysergide, and cyproheptadine.

Using animals with large electrolytic lesions of the median eminence-mediobasal hypothalamus, we confirmed earlier findings that metergoline (ME) and methysergide (MS) inhibit PRL secretion through activation of the dopamine receptors of the pituitary lactotrophs and established, in a quantitative manner, that their dopaminergic potencies are comparable to the potency of the dopamine receptor agonist, piribedil, with ED50 in the order of 0.35 to 0.22 mg/kg. Cyproheptadine (CYP), acting by an unknown mechanism, had only a weak inhibiting effect (ED50 greater than 20.0 mg/kg) in these experimental conditions. In the second part of the study, the PRL-inhibiting actions of ME, MS, CYP, and piribedil, respectively, were tested against the PRL release-stimulating effect of activation of the central serotonergic system that was induced by administration of a large dose of L-5-hydroxytryptophan (5HTP; 100 mg/kg), a small dose of 5HTP (15 mg/kg) in rats pretreated with fluoxetine, or by the serotonin receptor agonist quipazine (10.0 mg/kg, ip). The inhibiting potencies of ME (ED50 0.019, 0.014, and 0.048 mg/kg, respectively) against these three stimuli were much larger than in the lesioned animals or than the corresponding potencies of piribedil (ED50 2.2, 0.24, and 0.41 mg/kg, respectively). It is assumed that in these experimental conditions ME inhibited PRL release by blockade of the central serotonin receptors in addition to its dopaminergic effect and that at low doses (0.1 mg/kg or less) the entire inhibiting effect of ME was probably due to its antiserotonergic activity. With MS, which is a weaker serotonin receptor blocker than ME (ED50 0.178, 0.075, and 0.55 mg/kg, respectively, for the three serotonergic stimuli of PRL release), the antiserotonergic component in its PRL-inhibiting effect was evident but less clearly separable from the dopaminergic component in experiments with 5HTP and with fluoxetine plus 5HTP, whereas in experiments with quipazine the entire action could be accounted for by its dopaminergic activity. CYP was the least potent among the three blockers (ED50 0.6, 0.4, and 1.37 mg/kg, respectively, for the three serotonergic stimuli of PRL release), but appropriate tests indicated that it acted only as a serotonin receptor blocker and not by virtue of its antihistaminic, anticholinergic properties or by a direct action on the pituitary lactotrophs. SQ 10,631, another serotonin receptor blocker that was also tested, had no PRL-inhibiting activity. Because of the dual nature of the PRL-inhibiting mechanism of ME and MS and the low effectiveness of CYP, combined possibly with other actions, the serotonin receptor blockers have limited value in studies concerning the role of the central serotonergic system in the regulation of PRL secretion.

Animals↗
PubMed1980

Role of central nervous system neurotransmitters in mediating the effects of morphine on growth hormone- and prolactin-secretion in the rat.

Unanesthetized adult male rats with indwelling right atrial cannulae were used in the majority of experiments. Morphine (MOR, 3.0 mg/kg) caused a large but transient increase in both GH and PRL levels, which could be prevented with naloxone. Disruption of central noradrenergic function with diethyldithiocarbamate (400 mg/kg) or phenoxybenzamine (15 mg/kg) abolished the GH-releasing effect of MOR, without interfering with the PRL secretory response. Depletion of brain serotonin stores with p-chlorophenylalanine (300 mg/kg) or 5,7-dihydroxytryptamine or administration of serotonin receptor blocker, cyproheptadine (2.5 mg/kg), did not diminish the GH respnse to MOR but it inhibited, or in the case of 5,7-DHT treatment abolished the activation of PRL secretion. Additionally, metergoline (0.1 and 1.0 mg/kg), another serotonin receptor blocker, caused an inhibition of the GH-releasing action of MOR; however, this inhibition was reversed by pretreatment with spiroperidol (0.1 mg/kg). Metergoline also markedly diminished the MOR-induced elevation of PRL. Inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine (alpha-MT, 250 mg/kg) blunted the effect of MOR on GH; however, dopamine receptor blockers, spiroperidol (0.01 and 0.1 mg/kg) or (+)butaclamol (0.3 and 1.3 mg/kg), were without any influence. alpha-MT or spiroperidol did not alter the effect of MOR on PRL secretion, but the higher dose of (+)butaclamol suppressed it. It is concluded that the GH-releasing action of MOR requires unimpaired functioning of the central noradrenergic system, while the serotonergic and dopaminergic systems appear to play no significant role in it. In contrast, serotonergic systems seem to be essential for the activation of PRL secretion, whereas the noradrenergic system is not involved. It remains uncertain whether morphine activtes PRL secretion also through inhibition of dopaminergic activity. We favor the view that the dopaminergic component participates in the PRL activation by MOR, but that its contribution to the overall effect is rather small.

Animals↗
PubMed1980

Lack of evidence that the central serotoninergic system plays a role in the activation of prolactin secretion following inhibition of dopamine synthesis or blockade of dopamine receptors in the male rat.

Administration of alpha MT to inhibit catecholamine synthesis or dopamine (DA) receptor blockade with spiroperidol had no effect on the hypothalamic concentration of 5HT or 5HIAA. Fluoxetine to block serotonin uptake had no influence on the elevation of serum prolactin levels induced by alpha MT or DA receptor blockers and conversely alpha MT did not influence the prolactin-releasing action of 5HTP alone or in combination with fluoxetine. Depletion of brain serotonin stores with p-chlorophenylalanine did not affect the prolactin-releasing action of alpha MT or DA receptor blockers. In contrast, the serotonin blocker methysergide, but not cyproheptadine, inhibited the prolactin-releasing effect of alpha MT or alpha-flupentixol, a DA receptor blocker, but not of spiroperidol, another DA receptor blocker. The intensity of the inhibition induced by methysergide paralleled the intensity of inhibition induced by apomorphine. Methysergide conspicuously lowered serum prolactin in animals with electrolytic destruction of the median eminence, whereas cyproheptadine had only a slight effect. The prolactin-inhibiting effect of methysergide could be prevented by pretreatment of the lesioned rats with spiroperidol. It is concluded (1) that elimination of the influence of the DA system does not activate the central serotoninergic system; (2) that activity of the serotoninergic system has no role in the activation of prolactin secretion induced by suppression of the inhibitory dopaminergic influence, and (3) that the inhibiting action of methysergide on the prolactin-releasing effect of alpha MT or alpha-flupentixol is due to its dopamine receptor agonist activity rather than to blockade of serotonin receptors.

5-Hydroxytryptophan↗
PubMed1976

Differential effects of low doses of ethanol on the impulse activity in various regions of the limbic system.

This study was a follow-up to our earlier data which indicated that the hippocampus was one of the brain areas in which ethanol had a preferential action. Rabbits were chronically implanted with electrodes in 9 brain areas associated with the hippocampus. The EEG and multiple-unit activity were recorded simultaneously in each area before and for 15 min after i.p. injection of ethanol at dosages of 0, 150, 300, or 600 mg/kg, given in random order. Subjective evaluation of EEG tracings from all brain areas did not disclose any regional differences. The incidence of hippocampal theta rhythm was depressed transiently at the 2 lower doses and was increased in some rabbits at later post-injection times after the largest dose. Quantitative analysis of the unit activity revealed several major effects of ethanol. Individual rabbits varied significantly in their degree of response. The effects of ethanol included phasic decreases and increases, which varied with the brain area and the dose. A predominant depression of MUA occurred in the septum, fimbria/fornix, entorhinal cortex, and CA1 zone of the hippocampus. Large transient increases in MUA were noted in the CA1, hippocampal commissure, and entorhinal cortex. Overall, regional differences in unit activity consisted of a relatively greater effect in the septum, CA1, and the entorhinal cortex. Conspicuously smaller effects were evident in the CA3 and dentate zones of the hippocampus.

Animals↗