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

• Published in: The Journal of neuroscience Vol. 20; no. 24; pp. 9284 - 9289
• Main Authors: Valverde, Olga, Maldonado, Rafael, Valjent, Emmanuel, Zimmer, Anne M, Zimmer, Andreas
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 15.12.2000; Society for Neuroscience
• Subjects: Acute Disease; Addiction; Analysis of Variance; Animals; Aspectes moleculars; Autoradiography; Behavior, Animal - drug effects; Body Temperature - drug effects; Body Weight - drug effects; Brain - drug effects; Brain - metabolism; Cannabinoid; Cannabinoides; Chronic Disease; Drogoaddicció; Dronabinol - adverse effects; Drug Tolerance - genetics; Efectes fisiològics; Enkephalins - deficiency; Enkephalins - genetics; Enkephalins - metabolism; Enkephalins - pharmacology; Hyperalgesia - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation; Opioid; Piperidines - pharmacology; Protein Precursors - deficiency; Protein Precursors - genetics; Psychotropic Drugs - adverse effects; Pyrazoles - pharmacology; Receptors; Receptors, Cannabinoid; Receptors, Drug - antagonists & inhibitors; Receptors, Drug - metabolism; Substance Withdrawal Syndrome - genetics; Tolerance; Withdrawal
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.20-24-09284.2000

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 Delta9-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 Delta9-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 Delta9-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 Delta9-tetrahydrocannabinol and participates in the expression of cannabinoid abstinence.