Administration of MDMA to ethanol-deprived rats increases ethanol operant self-administration and dopamine release during reinstatement.
Recreational use of (±)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is often associated with other drugs, among which ethanol (EtOH) is one of the most common. However, little is known about how neurochemical sensitization produced by MDMA can modulate EtOH abuse. In this study we used EtOH operant self-administration tasks to investigate the effect of several low doses (0.33, 1.0 and 3.0 mg/kg) of MDMA in Dark Agouti rats. Motor activity was recorded after each MDMA administration. Changes in extracellular dopamine in the nucleus accumbens following a single EtOH injection (1.5 g/kg i.p.) were measured using intracerebral microdialysis in vivo after 1 wk of abstinence from EtOH, in order to mimic the dopaminergic response associated with reinstatement into EtOH consumption. Animals exposed to higher doses of MDMA (1.0 and 3.0 mg/kg) showed significantly enhanced EtOH self-administration during reinstatement and an increased EtOH-induced dopamine efflux. MDMA treatment acutely elevated motor activity after each administration in a dose-dependent manner. These findings suggest that repeated administration of MDMA, a relatively common drug of abuse, even at low doses, can alter subsequent vulnerability to EtOH consumption.
Moreno-Sanz
Guillermo
G
Department of Psychobiology, Faculty of Psychology, Campus de Somosaguas, Universidad Complutense de Madrid, Madrid, Spain.
O'Shea
Esther
E
Orio
Laura
L
Escobedo
Isabel
I
González-Cuevas
Gustavo
G
Navarro
Miguel
M
Colado
Maria Isabel
MI
López-Moreno
José Antonio
JA
D000428:Alcohol Drinking; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000097:blood; D003216:Conditioning, Operant / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D006213:Hallucinogens / Q000008:administration & dosage*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012646:Self Administration; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
D002492:Central Nervous System Depressants; D006213:Hallucinogens; D012701:Serotonin; D000431:Ethanol; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine