The rewarding properties of MDMA are preserved in mice lacking mu-opioid receptors.
The involvement of mu-opioid receptors in the rewarding properties of MDMA was explored in mu-opioid receptor knockout mice using the conditioning place preference paradigm. The associated release of dopamine in the nucleus accumbens was investigated by in vivo microdialysis. A significant rewarding effect of MDMA (10 mg/kg, i.p.) was observed in both wild-type and mu-opioid receptor knockout mice. MDMA (10 mg/kg, i.p.) also induced similar increases in dopamine and decreases in 3,4-dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens dialysates of both wild-type and mu-opioid receptor knockout mice. No significant differences in basal levels of dopamine, 3,4-dihydroxyphenylacetic or homovanillic acids between wild-type and mu-opioid receptor knockout mice were observed. In summary, the present results suggest that, in contrast to what has been reported for other drugs of abuse such as opioids, ethanol, nicotine and Delta(9)-tetrahydrocannabinol, mu-opioid receptors do not play a major role in the rewarding properties of MDMA. These differences could be due to distinct mechanisms controlling dopamine release in the nucleus accumbens and suggest that the effects of MDMA on dopaminergic neurons are independent of micro -opioid receptors.
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@upf.edu
Mendizabal
Victoria
V
Ortuño
Jordi
J
de la Torre
Rafael
R
Kieffer
Brigitte L
BL
Maldonado
Rafael
R
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012201:Reward; D013045:Species Specificity; D013997:Time Factors
D018759:Adrenergic Uptake Inhibitors; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine; D006719:Homovanillic Acid