*Present address: Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Universidat Pompeu Fabra, Dr. Aiguader 80, 08003 Barcelona, Spain.
Reduction of stress-induced analgesia but not of exogenous opioid effects in mice lacking CB1 receptors
Version of Record online: 9 OCT 2008
© European Neuroscience Association
European Journal of Neuroscience
Volume 12, Issue 2, pages 533–539, February 2000
How to Cite
Valverde, O., Ledent, C., Beslot, F., Parmentier, M. and Roques, B. P. (2000), Reduction of stress-induced analgesia but not of exogenous opioid effects in mice lacking CB1 receptors. European Journal of Neuroscience, 12: 533–539. doi: 10.1046/j.1460-9568.2000.00929.x
- Issue online: 9 OCT 2008
- Version of Record online: 9 OCT 2008
- Received 12 July 1999, revised 4 October 1999, accepted 20 October 1999
- CB1 receptors ;
- conditioned suppression of motility;
- opioid analgesia;
CB1 cannabinoid receptors are widely distributed in the central nervous system where they mediate most of the cannabinoid-induced responses. Here we have evaluated the interactions between the CB1 cannabinoid receptors and the endogenous opioid system by assaying a number of well-characterized opioid responses, e.g. antinociception and stress-mediated effects, on mutant mice in which the CB1 receptor gene was invalidated. The spontaneous responses to various nociceptive stimuli (thermal, mechanical and visceral pain) were not changed in mutant CB1 mice. Furthermore, the absence of the CB1 cannabinoid receptor did not modify the antinociceptive effects induced by different opioid agonists: morphine (preferential mu opioid agonist), d-Pen2-d-Pen5-enkephalin (DPDPE) and deltorphin II (selective delta opioid agonists), and U-50,488H (selective kappa opioid agonist) in the hot-plate and tail-immersion tests. In contrast, the stress-induced opioid mediated responses were modified in CB1 mutants. Indeed, these mutants did not exhibit antinociception following a forced swim in water at 34 °C and presented a decrease in the immobility induced by the previous exposure to electric footshock. However, the antinociception induced by a forced swim in water at 10 °C was preserved in CB1 mutants. These results indicate that CB1 receptors are not involved in the antinociceptive responses to exogenous opioids, but that a physiological interaction between the opioid and cannabinoid systems is necessary to allow the development of opioid-mediated responses to stress.