Methylenedioxymethamphetamine induces spontaneous tail-flicks in the rat via 5-HT 1A receptors

Abstract

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-HT 3 receptor antagonists, ICS 205, 930 and GR 38032F. They were attenuated by the mixed 5-HT 1/5-HT 2 receptor antagonist, methiotepin, the mixed 5-HT 1A/5-HT 1B receptor antagonist, (−)-alprenolol and the mixed 5-HT 1/5-HT 2 receptor antagonist, spiperone, but not by the selective 5-HT 1C/5-HT 2 receptor antagonists, ritanserin, ICI 169,369 and ketanserin. The novel 5-HT 1A receptor antagonists, BMY 7378 and NAN-190, each abolished MDMA-evoked spontaneous tail-flicks. Selective D 1, D 2, α 1, α 2, β 1 and β 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-HT 1A receptors. Thus, 5-HT 1A receptors appear to be involved in the acute functional actions of MDMA.