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Increase of morphine withdrawal in mice lacking A 2a receptors and no changes in CB 1 /A 2a double knockout mice
Author(s) -
Berrendero Fernando,
Castañé Anna,
Ledent Catherine,
Parmentier Marc,
Maldonado Rafael,
Valverde Olga
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02439.x
Subject(s) - knockout mouse , cannabinoid receptor , receptor , adenosine a2a receptor , opioid , (+) naloxone , cannabinoid , endocannabinoid system , medicine , physical dependence , endocrinology , psychology , morphine , chemistry , adenosine receptor , biology , antagonist , agonist
CB 1 cannabinoid and A 2a adenosine receptors are highly expressed in the central nervous system where they modulate numerous physiological processes including emotional behaviour and the responses of several drugs of abuse. To investigate the contribution of these receptors in emotional‐like responses and opioid dependence we have generated CB 1 /A 2a double deficient mice ( \mathrm{CB}^{‐/‐}_{1} / \mathrm{A}^{‐/‐}_{2\mathrm{a}} ). The spontaneous locomotor activity was reduced in double knockout as compared to wild‐type animals. Emotional‐like responses of \mathrm{CB}^{‐/‐}_{1} / \mathrm{A}^{‐/‐}_{2\mathrm{a}} mice were investigated using the elevated plus‐maze and the lit‐dark box. Mutant mice exhibited an increased level of anxiety in both behavioural models. The specific involvement of CB 1 and A 2a receptors in morphine dependence was evaluated by using A 2a knockout mice and CB 1 /A 2a double mutant mice. The severity of naloxone‐precipitated morphine withdrawal syndrome was significantly increased in the absence of A 2a adenosine receptors whereas no modifications were observed in the double knockout mice. These results suggest that both receptors participate in the control of emotional behaviour and seem to play an opposite role in the expression of opioid physical dependence.