PT  - JOURNAL ARTICLE
AU  - Olga Valverde
AU  - Rafael Maldonado
AU  - Emmanuel Valjent
AU  - Anne M. Zimmer
AU  - Andreas Zimmer
TI  - Cannabinoid Withdrawal Syndrome Is Reduced in Pre-Proenkephalin Knock-Out Mice
AID  - 10.1523/JNEUROSCI.20-24-09284.2000
DP  - 2000 Dec 15
TA  - The Journal of Neuroscience
PG  - 9284--9289
VI  - 20
IP  - 24
4099  - http://www.jneurosci.org/content/20/24/9284.short
4100  - http://www.jneurosci.org/content/20/24/9284.full
SO  - J. Neurosci.2000 Dec 15; 20
AB  - 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 Δ9-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 Δ9-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 Δ9-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 Δ9-tetrahydrocannabinol and participates in the expression of cannabinoid abstinence.