Elevation of serum prolactin and corticosterone concentrations in the rat after the administration of 3,4-methylenedioxymethamphetamine.
The racemic mixture of 3,4-methylenedioxymethamphetamine (MDMA), which has been reported to produce selective destruction of serotonergic neurons in the central nervous system, was studied to determine its neuroendocrine and temperature effects and mechanism of action. MDMA elevated serum concentrations of corticosterone in doses ranging from 3 to 20 mg/kg administered i.p. Serum corticosterone concentrations were elevated 30 min after the administration of MDMA (10 mg/kg i.p.) and remained elevated 4 hr later. Serum prolactin (PRL) concentrations were elevated by administration of MDMA in doses ranging from 1 to 20 mg/kg i.p., and were maximal 60 min after the injection of 10 mg/kg i.p., declining rapidly over the next 4 hr. MDMA also significantly elevated the body temperature of rats maintained at ambient (23 degrees C) temperature. MDMA-induced corticosterone secretion and hyperthermia were blocked by the 5-hydroxytryptamine (5-HT) antagonists, ketanserin and mianserin, which have a high affinity for 5-HT2 binding sites. Conversely, neither (-)-pindolol, a beta antagonist that also blocks 5-HT1A-mediated responses, nor the nonspecific 5-HT antagonists, cyproheptadine and metergoline, had an effect on MDMA-induced corticosterone secretion. None of the 5-HT antagonists blocked MDMA-induced PRL secretion. Pretreatment with fluoxetine (10 mg/kg i.p.) 16 hr before MDMA administration significantly blunted the effect of MDMA on corticosterone but not PRL secretion. Pretreatment with p-chlorophenylalanine (150 mg/kg i.p.) for 3 days depleted cortical and hypothalamic 5-HT and 5-hydroxyindoleacetic acid by approximately 80% and significantly attenuated MDMA-induced corticosterone and PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D010134:Fenclonine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D011388:Prolactin / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology
D000662:Amphetamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005473:Fluoxetine; D015104:3,4-Methylenedioxyamphetamine; D011388:Prolactin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D010134:Fenclonine; D003345:Corticosterone