Study of the behavioural responses related to the potential addictive properties of MDMA in mice.
We investigated several behavioural responses induced by repeated administration of MDMA in mice that could be related to its potential abuse liability. Mice treated with MDMA at the dose of 10 mg/kg displayed a significant conditioned place preference with respect to saline treated controls, while lower doses (0.3, 1.0, 3.3 mg/kg) had no effect. The development of physical dependence was also investigated. Mice were treated with MDMA (10 mg/kg) twice daily for 5 days. On day 6, following a single administration of MDMA mice received the following monoaminergic antagonists: metergoline (0.1 and 1 mg/kg), ritanserin (0.25 and 1 mg/kg), timolol (2 and 10 mg/kg), prazosin (0.25 and 1 mg/kg), SCH 23390 (0.05 and 0.25 mg/kg), raclopride (0.1 and 0.5 mg/kg) or vehicle, and several somatic manifestations of withdrawal were evaluated for 45 min. Metergoline induced paw tremor, face rubbing, as well as an increase in locomotor activity in mice chronically treated with MDMA. Ritanserin, and timolol induced only paw tremor, while SCH 23390 and raclopride did not produce any somatic manifestation indicative of abstinence. The possible modification of the rewarding properties of MDMA (10 mg/kg) by the monoaminergic antagonists producing the most relevant somatic signs of withdrawal namely, metergoline (0.1 and 1 mg/kg) and timolol (2 and 10 mg/kg) were tested in the conditioned place preference paradigm. Results showed that metergoline did not significantly modify the rewarding properties of MDMA, whereas only the highest dose of timolol was able to decrease MDMA reward. No signs of dopaminergic neurotoxicity were observed following chronic treatment with MDMA as revealed by [(3)H] mazindol binding. The possible motivational and affective components of the withdrawal syndrome were assessed in the suppression of operant responding for food, the conditioned place aversion, and the lit/dark paradigms. Results showed that the somatic symptoms observed were not accompanied by any aversive/dysphoric or anxiogenic-like behaviours. These results reveal the rewarding properties of MDMA in mice, and suggest that chronic MDMA administration does not induce classical manifestations of physical dependence in mice.
Robledo
Patricia
P
Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, c/ Dr. Aiguader 80, 08003 Barcelona, Spain. patricia.robledo@cexs.upf.es
Balerio
Graciela
G
Berrendero
Fernando
F
Maldonado
Rafael
R
D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage* / Q000378:metabolism*; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D020891:Raclopride / Q000378:metabolism / Q000494:pharmacology
D020891:Raclopride; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D011224:Prazosin