Search

Lysergic acid diethylamide (LSD), 0.05 mg/kg and 0.20 mg/kg, significantly decreased plasma prolactin (PRL) levels in male rats. LSD, 0.20 mg/kg, also inhibits the increase in plasma PRL levels produced by chlorpromazine (CPZ), 5 mg/kg, and alpha-methyl-paratyrosine (AMPT), 50 mg/kg, both of which interfere with dopaminergic inhibition of PRL secretion. LSD was more potent than methysergide, a serotonin receptor blocker, in lowering plasma PRL levels and more potent than apomorphine, a known direct acting dopamine agonist, in blocking the increase in plasma PRL produced by quipazine, a 5-HT agonist. These results suggest LSD has potent dopamine agonist properties on the rat pituitary or hypothalamic dopamine receptors which directly or indirectly inhibit PRL secretion.

The hallucinogenic indoleamine drugs N,N-dimethyltryptamine (N,N-DMT), psilocybin, bufotenin, 5-methoxy-N,N-dimethyltryptamine, and N-methyltryptamine, increased rat plasma prolactin (PRL) levels. The increase in plasma PRL produced by N,N-DMT, psilocybin, and bufotenin was inhibited by methysergide, a serotonin receptor blocker. Parachlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, significantly potentiated the increase in PRL produced by N,N-DMT, and psilocybin. Parachloroamphetamine, a relatively selective toxin for serotonin neurons, also stimulated the increase in PRL produced by N,N-DMT. These results suggest that the indole hallucinogens stimulate PRL secretion by a serotonergic agonist mechanism. Bufotenin has been reported to pass the blood-brain barrier poorly, but of the indoles studied it had the most potent effect on PRL secretion. This raises the possibility that the serotonin receptors which promote PRL secretion may be outside the blood-brain barrier or that the central 5-HT receptors which mediate PRL secretion may be especially responsive to bufotenin.

Cis (alpha)-flupenthixol and (+)-butaclamol are effective anti-psychotic agents but trans (beta)-flupenthixol and (-)-butaclamol are not. alpha-Flupenthixol was found to be 245 times more active in elevating rat plasma prolactin than the beta-isomer. The discrepancy between (+)-butaclamol and (-)-butaclamol was even greater. These results support the hypothesis that the dopamine receptors that mediate the effects of dopamine on prolactin secretion are similar to those that mediate the anti-psychotic effect of neuroleptic drugs.

A previous report indicated that the tricyclic antidepressants imipramine and amitriptyline markedly increased plasma prolactin levels in man. We found no increases after acute or chronic treatment with either drug in usual clinical doses. The results indicate that blockade of serotonin reuptake does not affect basal prolactin levels in man.