The effects of MDMA pretreatment on the behavioural effects of other drugs of abuse in the rat elevated plus-maze test.
Few preclinical studies have found long-term behavioural consequences of the serotonergic neurotoxicity produced by 3,4-methylenedioxymethamphetamine (MDMA). This study investigated whether pretreatment with MDMA altered the behavioural effects of other drugs of abuse. Adult male Lister hooded rats (n=10/group) were pretreated with 10 mg/kg MDMA or 1 ml/kg saline vehicle intraperitoneally every 2 h for 6 h. Fourteen days later, the behavioural effects of d-amphetamine (2 mg/kg), cocaine (10 mg/kg), ethanol (2.0 g/kg), heroin (0.5 mg/kg), or MDMA (10 mg/kg) were assessed in the elevated plus-maze test. MDMA pretreatment produced approximately 20-25% decrease in hippocampal 5-HT and 5-HIAA concentrations, and [(3)H]paroxetine binding when analysed 2 weeks later. Despite inducing neurotoxicity, this regimen had no effect upon the plus-maze behaviour induced by ethanol, heroin, and MDMA. Acutely, and independent of neurotoxic pretreatment, MDMA produced a clear anxiogenic-like behavioural profile with a reduction of open arm entries and suppression of explorative behaviours. Despite being acutely anxiogenic, pretreatment with a neurotoxic regimen of MDMA has little effect on the anxiety-related effects of other drugs of abuse. It is possible that extended time points would produce significant changes, although the available evidence suggests that the plus-maze may not be a suitable model for detection of behavioural dysfunction after neurotoxic MDMA.
Sumnall
H R
HR
Department of Psychology, Eleanor Rathbone Building, University of Liverpool, Liverpool L69 7ZA, UK.
O'Shea
E
E
Marsden
C A
CA
Cole
J C
JC
D000818:Animals; D001007:Anxiety / Q000378:metabolism; D004347:Drug Interactions; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D013287:Illicit Drugs / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage* / Q000378:metabolism; D017374:Paroxetine / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D051381:Rats
D013287:Illicit Drugs; D017374:Paroxetine; D018817:N-Methyl-3,4-methylenedioxyamphetamine