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Biphasic effect of 5-methoxy-N,N-dimethyltryptamine on rat prolactin secretion.

M Simonovic, H Y Meltzer

Brain research August 8, 1983 DOI: 10.1016/0006-8993(83)90573-5 via PubMed

Summary

AI-generated from the abstract

5-MeODMT, a serotonin receptor agonist, has a two-phase effect on prolactin secretion in rats. It initially causes a short, dose-dependent increase in serum prolactin levels, lasting less than 30 minutes. After 30 minutes, it inhibits prolactin release stimulated by other serotonin agonists, alpha-methylparatyrosine, or low-dose haloperidol, but does not alter the effect of gamma-butyrolactone or high-dose haloperidol. The initial rise likely results from activating postsynaptic serotonin receptors, while the later inhibition appears due to increased activity of dopamine neurons. This biphasic pattern is also seen with quipazine but not with 5-MeOT, which does not cross the blood-brain barrier.

Study at a glance

Characteristics Experimental study Peer reviewed
Population Rats
Interventions 5-MeODMT 5-methoxytryptamine alpha-methylparatyrosine haloperidol gamma-butyrolactone quipazine
Dose 2.5-10 mg/kg, 1-15 mg/kg, 10 mg/kg, 50 mg/kg, 0.15 mg/kg, 1 mg/kg, 500 mg/kg
Citations 12
Key finding 5-MeODMT exerts a biphasic effect on rat prolactin secretion: initial short-term stimulation followed by inhibition of stimulated release, likely mediated by serotonin and dopamine pathways respectively.

Abstract

5-Methoxy-N,N-dimethyltryptamine (5-MeODMT), a potent serotonin (5-HT) receptor agonist, exerts a biphasic effect on rat prolactin (PRL) secretion. 5-MeODMT (2.5-10 mg/kg) produces a marked, dose-related but short-lasting (less than 30 min) rise in serum PRL levels. At intervals longer than 30 min, 5-MeODMT (1-15 mg/kg) inhibits the stimulation of PRL secretion by another 5-HT agonist, 5-methoxytryptamine (5-MeOT, 10 mg/kg), by alpha-methylparatyrosine (50 mg/kg) or by haloperidol (0.15 mg/kg). 5-MeODMT did not significantly alter the PRL-releasing effect of gamma-butyrolactone (500 mg/kg) or a higher dose of haloperidol (1 mg/kg). The biphasic effect of 5-MeODMT on rat PRL secretion is shared by the centrally-acting 5-HT agonist quipazine, but not by 5-MeOT, an indole derivative excluded by the blood-brain barrier. The initial stimulation of PRL secretion by 5-MeODMT is probably due to its ability to activate postsynaptic 5-HT receptors. The subsequent inhibitory effect of 5-MeODMT appears to be due to increased functional activity of tuberoinfundibular dopamine neurons. The possible mechanisms underlying the inhibitory effect of 5-MeODMT on PRL release are discussed.

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