Reduced social interaction following 3,4-methylenedioxymethamphetamine is not associated with enhanced 5-HT 2C receptor responsivity

Abstract

This study examined the long-term change in serotonergic (5-hydroxytryptamine, 5-HT) neuronal function and 5-HT(2C) receptor agonist-induced behaviour following treatment of young rats with 3,4-methylenedioxymethamphetamine (MDMA). On post-natal day (PND) 28, Lister-hooded rats received either MDMA (15 mg/kg i.p.) or saline (1 ml/kg i.p.) twice daily for 3 days. On PND 50 social interaction was assessed between treatment-matched pairs of rats derived from separate litters. The effect of either the 5-HT(2C) receptor agonist, m-chlorophenylpiperazine (m-CPP, 2.5 or 1 mg/kg i.p., respectively) or saline was examined on open-field exploration (PND 52) and elevated plus-maze behaviour (PND 56). Acutely, MDMA produced hyperlocomotion and hypothermia compared with saline injection (p<0.001). Following 20 days abstinence, social interaction was decreased by 26% (p<0.05) in MDMA pre-treated rats compared with saline controls, without any change in locomotion. There was no difference in open-field or elevated plus-maze behaviour between pre-treatment groups. m-CPP caused hypolocomotion in the open-field and decreased both the percentage entries into, and time spent in, the open arms of the elevated plus-maze to a comparable extent in MDMA and saline pre-treated rats. Hippocampal and frontal cortical 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) were significantly reduced in MDMA pre-treated rats, without any change in [(3)H]paroxetine binding or plasma corticosterone levels. These data suggest that the MDMA-induced reduction in social interaction is not mediated via alteration of 5-HT(2C) receptor function.