The effect of 3,4-methylenedioxymethamphetamine ('Ecstasy') on serotonergic regulation of the mammalian circadian clock mechanism in rats: the role of dopamine and hyperthermia.
The recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is known to be a neurotoxin for serotonergic axons ascending from the raphe nucleus including those which terminate on neurons of the suprachiasmatic nuclei (SCN) of the hypothalamus, the putative mammalian circadian clock. Since dopamine release has been implicated in the serotonergic neurotoxicity, we examined the effects of the dopamine synthesis inhibitor alpha-methyl-p-tyrosine (AMPT) and the D2 receptor antagonist haloperidol (HAL) on the long-term effect of MDMA on serotonergic regulation of the SCN neuronal firing rhythm. Co-administration of AMPT or HAL with MDMA eliminated the acute hyperthermic response but had no effect on the MDMA-induced phase shift in the firing rhythm of SCN neurons to the selective 5-HT1A receptor agonist, 8-hydroxy-2-(dipropylamino)-tetralin. It is concluded that neither dopamine metabolism nor hyperthermia account for the altered serotonergic function in the SCN produced by MDMA. Toxic free radical production following MDMA metabolism may be responsible.
Dafters
Richard I
RI
Psychology Department, 58 Hillhead Street, Glasgow University, Glasgow, G12 8QB, UK. r.dafters@psy.gla.ac.uk
Biello
Stephany M
SM
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism
D018492:Dopamine Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine