Effects of the selective 5-HT2A receptor antagonist MDL 100,907 on MDMA-induced locomotor stimulation in rats.
J H Kehne, H J Ketteler, T C McCloskey, C K Sullivan, M W Dudley, C J Schmidt
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology August 1996 DOI: 10.1016/0893-133x(95)00160-f (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Peer reviewed |
|---|---|
| Interventions | MDMA MDL 100 907 ritanserin clozapine MDL 28 133A methiothepin propranolol haloperidol SCH 23390 5 7-dihydroxytryptamine |
| Topics | MDMA Serotonin |
| Key points | The authors conclude that serotonin released onto 5-HT2A receptors contributes to MDMA-stimulated locomotion, since the selective 5-HT2A antagonist MDL 100,907 reduced MDMA-stimulated locomotion without affecting basal locomotion, and serotonin depletion with 5,7-dihydroxytryptamine also attenuated it. They suggest MDMA-stimulated locomotion may be a useful in vivo behavioral measure of 5-HT2A antagonism, and note contributions of 5-HT1A, D1, and D2 receptors. |
Abstract
(+/-)3,4-Methylenedioxymethamphetamine (MDMA) releases dopamine and serotonin in vivo and stimulates locomotor activity. Previous work demonstrated that MDMA-stimulated dopamine release could be reduced by the selective 5-HT2A receptor antagonist [R-(+)-a- (2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinem ethanol] (MDL 100,907). In the present study MDL 100,907 significantly reduced MDMA-stimulated locomotion without affecting basal levels of locomotion. Other agents with 5-HT2A antagonist activity (ritanserin, clozapine, MDL 28,133A, or methiothepin), as well as agents that block 5-HT1A-(propranolol), D2-(haloperidol), or D1 receptors (SCH 23390) also reduced MDMA-stimulated locomotion. Intraventricularly administered 5,7-dihydroxytryptamine decreased regional 5-HT levels and attenuated MDMA-stimulated locomotion. These data support the conclusion that serotonin released onto 5-HT2A receptors contributes to MDMA-stimulated locomotion and suggest that MDMA-stimulated locomotion may be useful as an in vivo behavioral measure of 5-HT2A antagonism. The data also support previous reports of contributions of 5-HT1A, D1 and D2 receptors to MDMA-stimulated locomotion. A preliminary time-course analysis indicating time-dependent contributions of different receptors to MDMA-stimulated locomotion suggests the potential utility of this model for characterizing potential atypical antipsychotic compounds.