Methylenedioxymethamphetamine induces spontaneous tail-flicks in the rat via 5-HT1A receptors.
In rats lightly restrained in horizontal cylinders, (+/-)-3,4-methylenedioxymethamphetamine (MDMA) dose dependently (0.16-10.0 mg/kg, s.c.) elicited spontaneous tail-flicks; that is, tail-flicks in the absence of extraneous stimulation. In contrast, amphetamine over a similar dose-range was inactive. Selective inhibitors of 5-hydroxytryptamine (5-HT) uptake and carrier-mediated 5-HT release, paroxetine and citalopram, did not induce spontaneous tail-flicks themselves and blocked those induced by MDMA. In distinction, maprotiline and bupropion, selective inhibitors of noradrenaline and dopamine uptake, respectively, failed to modify the action of MDMA. Spontaneous tail-flicks elicited by MDMA were unaffected by the selective 5-HT3 receptor antagonists, ICS 205,930 and GR 38032F. They were attenuated by the mixed 5-HT1/5-HT2 receptor antagonist, methiotepin, the mixed 5-HT1A/5-HT1B receptor antagonist, (-)-alprenolol and the mixed 5-HT1A/5-HT2 receptor antagonist, spiperone, but not by the selective 5-HT1C/5-HT2 receptor antagonists, ritanserin, ICI 169,369 and ketanserin. The novel 5-HT1A receptor antagonists, BMY 7378 and NAN-190, each abolished MDMA-evoked spontaneous tail-flicks. Selective D1, D2, alpha 1, alpha 2, beta 1 and beta 2 antagonists had little influence upon induction of spontaneous tail-flicks by MDMA. These data indicate that MDMA evokes spontaneous tail-flicks in the rat via a release of 5-HT which acts at 5-HT1A receptors. Thus, 5-HT1A receptors appear to be involved in the acute functional actions of MDMA.
Neurobiology Division, Fondax-Groupe de Recherche Servier, Puteaux, France.
M J
MJ
Millan
F C
FC
Colpaert
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D017374:Paroxetine; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists; D013623:Tail / Q000502:physiology*
D018492:Dopamine Antagonists; D010880:Piperidines; D012702:Serotonin Antagonists; D012701:Serotonin; D017374:Paroxetine; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine