Cannabinoid withdrawal syndrome is reduced in pre-proenkephalin knock-out mice.
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.
Valverde
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O
Laboratori de Neuropharmacologia, Facultat de Ciéncies de la Salut i de la Vida, Universidat Pompeu Fabra, 08003 Barcelona, Spain.
Maldonado
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R
Valjent
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Zimmer
A M
AM
Zimmer
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A
D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D013759:Dronabinol / Q000009:adverse effects*; D004361:Drug Tolerance / Q000235:genetics; D004745:Enkephalins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D006930:Hyperalgesia / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010880:Piperidines / Q000494:pharmacology; D011498:Protein Precursors / Q000172:deficiency* / Q000235:genetics; D011619:Psychotropic Drugs / Q000009:adverse effects*; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant; D013375:Substance Withdrawal Syndrome / Q000235:genetics*
D004745:Enkephalins; D010880:Piperidines; D011498:Protein Precursors; D011619:Psychotropic Drugs; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol; C033660:preproenkephalin; D000077285:Rimonabant