Behavioural manifestations induced by noradrenergic, dopaminergic and serotonergic antagonists in chronically MDMA (“ecstasy”) treated mice

GRACIELA BALERIO, PATRICIA ROBLEDO AND RAFAEL MALDONADO

Brighton, UK

Workshop; International Workshop on New Advances in the Understanding and treatment of Addiction; 2002

Behavioural manifestations induced by noradrenergic, dopaminergic and serotonergic antagonists in chronically MDMA (“ecstasy”) treated mice. Graciela Balerio, Patricia Robledo and Rafael Maldonado. Laboratori de Neurofarmacologia. Departament de Ciències Experimentals i de la Salut. Universitat Pompeu Fabra. Barcelona. SPAIN. MDMA is a psychoactive drug of abuse which is increasingly popular in human recreational use. In laboratory animals, MDMA increases locomotion, decreases exploratory behaviour, disrupts startle plasticity and schedule-controlled responding, and has been implicated in serotonin (5-HT) neurotoxicity. However, the ability of MDMA to induce physical dependence remains to be clarified. In the present study, we investigated the possible development of physical dependence in mice chronically treated with MDMA by evaluating behavioural manifestations that could be related to a withdrawal syndrome. Mice were treated with MDMA (10 mg/kg, i.p.) twice daily (9:30 and 18:30 h) for 5 days. The 6th day, mice received a single dose of MDMA (10 mg/kg, i.p.) at 9:30 and four hours later animals received an acute injection of either the mixed b1 and b2 adrenergic antagonist, timolol (2 and 10 mg/kg, i.p.), the selective a1 adrenergic antagonist, prazosin (0.25 and 1 mg/kg, i.p.), the D1 dopamine antagonist, SCH 23390 (0.05 and 0.25 mg/kg, i.p.), the D2 dopamine antagonist, raclopride (0.1 and 0.5 mg/kg, i.p.), the non-selective 5-HT antagonist, metergoline (0.1 and 1 mg/kg, i.p.), the 5-HT2 antagonist, ritanserin (0.25 and 1 mg/kg, i.p.) or vehicle. Inmediately following the administration of the antagonists, several behavioural manifestations of a possible withdrawal syndrome were evaluated for 45 min. Results showed that the administration of the b adrenergic antagonist and both 5-HT antagonists in mice chronically treated with MDMA displayed some behavioural alterations such as paw tremor and face rubbing. Prazosin, SCH 23390 and raclopride did not produce any behavioural manifestation of withdrawal in MDMA treated mice. These results suggest that the blockade of b adrenergic or 5-HT receptors produces behavioural alterations in mice chronically treated with MDMA.