title: Delta9-tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins: reduction in morphine withdrawal syndrome without change in rewarding effect.
abstract: Recent studies have suggested that cannabinoids might initiate the consumption of other highly addictive substances, such as opiates. In this work, we show that acute administration of Delta9-tetrahydrocannabinol in mice facilitates the antinociceptive and antidepressant-like responses elicited by the endogenous enkephalins protected from their degradation by RB 101, a complete inhibitor of enkephalin catabolism. This emphasizes the existence of a physiological interaction between endogenous opioid and cannabinoid systems. Accordingly, Delta9-tetrahydrocannabinol increased the release of Met-enkephalin-like material in the nucleus accumbens of awake and freely moving rats measured by microdialysis. In addition, this cannabinoid agonist displaced the in vivo [3H]diprenorphine binding to opioid receptors in total mouse brain. The repetitive pretreatment during 3 weeks of Delta9-tetrahydrocannabinol in mice treated chronically with morphine significantly reduces the naloxone-induced withdrawal syndrome. However, this repetitive administration of Delta9-tetrahydrocannabinol did not modify or even decrease the rewarding responses produced by morphine in the place preference paradigm. Taken together, these behavioural and biochemical results demonstrate the existence of a direct link between endogenous opioid and cannabinoid systems. However, chronic use of high doses of cannabinoids does not seem to potentiate the psychic dependence to opioids.
authors.affiliation: Département de Pharmacochimie Moléculaire et Structurale, U266 INSERM, UMR 8600 CNRS, UFR des Sciences Pharmaceutiques et Biologiques, 4, Avenue de l'Observatoire, 75270 Paris Cedex 06, France.
authors.forename: O
authors.initials: O
authors.lastname: Valverde
authors.forename: F
authors.initials: F
authors.lastname: Noble
authors.forename: F
authors.initials: F
authors.lastname: Beslot
authors.forename: V
authors.initials: V
authors.lastname: Daugé
authors.forename: M C
authors.initials: MC
authors.lastname: Fournié-Zaluski
authors.forename: B P
authors.initials: BP
authors.lastname: Roques
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004174:Diprenorphine / Q000493:pharmacokinetics; D004220:Disulfides / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology*; D004347:Drug Interactions / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000187:drug effects* / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009292:Narcotic Antagonists / Q000493:pharmacokinetics; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000503:physiopathology; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D000700:Analgesics; D004220:Disulfides; D009292:Narcotic Antagonists; D009294:Narcotics; D011619:Psychotropic Drugs; D014316:Tritium; C074024:RB 101; D004174:Diprenorphine; D010649:Phenylalanine; D004744:Enkephalin, Methionine; D009020:Morphine; D013759:Dronabinol