Effects of repeated MDMA administration on the motivation for palatable food and extinction of operant responding in mice

Abstract

Repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) produces mainly dopaminergic neurotoxicity in mice. However, the consequences of this exposure on the behavioural responses related to natural reinforcing stimuli are still largely unknown. We examined whether repeated treatment with neurotoxic and non-neurotoxic doses of MDMA could exert acute and long-lasting effects on the motivation of mice to obtain a highly palatable food and on the extinction and reinstatement of food-seeking behaviour. Food-deprived mice were first trained to acquire stable responding on fixed ratio (FR) schedules of reinforcement and then treated twice daily with saline, 3 or 30 mg/kg MDMA during four consecutive days. The high dose of MDMA impaired instrumental responding on the first and third day of treatment, whilst no residual effects were apparent on FR5 responding at any of the doses studied 24 h after treatment withdrawal. Breaking points were decreased in mice treated with both doses of MDMA. This decrease in motivation for palatable food was not due to unspecific locomotor or coordination deficits. A resistance to extinction was observed only with the highest dose of MDMA, whilst all mice showed similar reinstatement of palatable food-seeking behaviour irrespective of previous treatment. Autoradiography of [3H]-mazindol binding revealed a decrease in striatal dopamine transporter binding only in mice treated with the highest dose of MDMA. This study demonstrates that repeated treatment with MDMA decreases the incentive motivation for a palatable food reward and that long-lasting MDMA-induced dopaminergic neurotoxicity increases the resistance to extinction of responding in the absence of reward.