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The Journal of Neuroscience, December 15, 2000, 20(24):9284-9289

Cannabinoid Withdrawal Syndrome Is Reduced in Pre-Proenkephalin Knock-Out Mice

Olga Valverde¹, Rafael Maldonado¹, Emmanuel Valjent¹, Anne M. Zimmer², and Andreas Zimmer²

¹ Laboratori de Neuropharmacologia, Facultat de Ciéncies de la Salut i de la Vida, Universidat Pompeu Fabra, 08003 Barcelona, Spain, and ² Laboratory of Genetics, National Institute of Mental Health, Bethesda, Maryland 20892

The functional interactions between the endogenous cannabinoid and opioid systems were evaluated in pre-proenkephalin-deficient mice. Antinociception induced in the tail-immersion test by acute 9-tetrahydrocannabinol was reduced in mutant mice, whereas no difference between genotypes was observed in the effects induced on body temperature, locomotion, or ring catalepsy. During a chronic treatment with 9-tetrahydrocannabinol, the development of tolerance to the analgesic responses induced by this compound was slower in mice lacking enkephalin. In addition, cannabinoid withdrawal syndrome, precipitated in 9-tetrahydrocannabinol-dependent mice by the injection of SR141716A, was significantly attenuated in mutant mice. These results indicate that the endogenous enkephalinergic system is involved in the antinociceptive responses of 9-tetrahydrocannabinol and participates in the expression of cannabinoid abstinence.

Key words: cannabinoid; opioid; mice; mutation; withdrawal; addiction; tolerance

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20249284-06$05.00/0

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