Decreased social behaviour following 3,4-methylenedioxymethamphetamine (MDMA) is accompanied by changes in 5-HT2A receptor responsivity.
This study examined the involvement of the 5-HT(2A) receptor in the long-term anxiogenic effect of a brief exposure of young rats to 3,4-methylenedioxymethamphetamine (MDMA) using the social interaction and elevated plus-maze paradigms. Wistar rats (post-natal day (PND) 28) received either MDMA (5 mg/kg i.p.) or saline (1 ml/kg i.p.) hourly for 4 h on 2 consecutive days. Locomotor activity was measured for 60 min after the first injection and core body temperature was recorded at regular intervals over 4 h. On PND 84, without further drug administration, social interaction was assessed between treatment-matched rat pairs derived from separate litters. On PND 86, rats received either the 5-HT(2A/2C) receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg i.p.) or saline and locomotor activity, wet-dog shakes and back muscle contractions were monitored. The change in elevated plus-maze behaviour was assessed following the same injection on PND 87. Acutely, MDMA produced a significant hyperlocomotion and hyperthermia (p<0.01). Following 55 days of abstinence, social interaction was reduced by 27% in MDMA pre-treated rats compared with that in controls (p<0.01). On the elevated plus-maze, pre-treatment with MDMA prevented the anxiogenic effect of DOI. On PND 92, hippocampal, frontal cortical and striatal 5-hydroxytryptamine (5-HT) was significantly reduced in MDMA pre-treated rats by between 16% and 22%, without any accompanying change in [(3)H]paroxetine binding in cortical homogenates. In conclusion, exposure of young rats to repeated MDMA caused serotonin depletion and induced 'anxiety-like' behaviour in the social interaction test accompanied by a long-lasting reduction in specific 5-HT(2A) receptor mediated behaviour.
Bull
Eleanor J
EJ
Institute of Neuroscience, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK. mbxejb@nottingham.ac.uk
Hutson
Peter H
PH
Fone
Kevin C F
KC
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists; D012919:Social Behavior
D000662:Amphetamines; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine