Reduced social interaction following 3,4-methylenedioxymethamphetamine is not associated with enhanced 5-HT 2C receptor responsivity.
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.
Bull
E J
EJ
School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.
Hutson
P H
PH
Fone
K C F
KC
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D005106:Exploratory Behavior / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced; D066298:In Vitro Techniques; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D017374:Paroxetine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000009:adverse effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012919:Social Behavior; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000523:psychology
D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017374:Paroxetine; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C015068:1-(3-chlorophenyl)piperazine; D003345:Corticosterone