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Publication : Increase of morphine withdrawal in mice lacking A2a receptors and no changes in CB1/A2a double knockout mice.

First Author  Berrendero F Year  2003
Journal  Eur J Neurosci Volume  17
Issue  2 Pages  315-24
PubMed ID  12542668 Mgi Jnum  J:108014
Mgi Id  MGI:3622855 Doi  10.1046/j.1460-9568.2003.02439.x
Citation  Berrendero F, et al. (2003) Increase of morphine withdrawal in mice lacking A2a receptors and no changes in CB1/A2a double knockout mice. Eur J Neurosci 17(2):315-24
abstractText  CB1 cannabinoid and A2a 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 CB1/A2a double deficient mice (CB1-/-/A2a-/-). The spontaneous locomotor activity was reduced in double knockout as compared to wild-type animals. Emotional-like responses of CB1-/-/A2a-/- 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 CB1 and A2a receptors in morphine dependence was evaluated by using A2a knockout mice and CB1/A2a double mutant mice. The severity of naloxone-precipitated morphine withdrawal syndrome was significantly increased in the absence of A2a 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.
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