title: Possible involvement of endocannabinoids in the increase of morphine consumption in maternally deprived rat.
abstract: Whether adolescent exposure to chronic delta-9-tetrahydrocannabinol (THC) facilitates progression to opioid consumption is still controversial. In a maternal deprivation model (3 h daily from postnatal day 1-14), we previously reported that adolescent exposure to chronic THC blocks morphine dependence in maternally deprived (D) rats. Owing to the existence of a functional cross-interaction between the opioid and cannabinoid systems in reward, we evaluated if the vulnerability to opiate reward in D rats, may involve an alteration of the endocannabinoid system. Anandamide and 2-arachidonoylglycerol (2-AG), were quantified in the striatum and mesencephalon of adolescent and adult D and non-deprived (animal facility rearing, AFR) rats by isotope dilution liquid chromatography-mass spectrometry. Oral morphine self-administration behavior was analyzed for 14 weeks, 24 days after chronic injection of the cannabinoid CB1 receptor antagonist/inverse agonist, SR141716A (3 mg/kg) for 2 weeks during adolescence (PND 35-48). Adolescent D rats exhibited higher basal levels of anandamide than adolescent AFR rats in the nucleus accumbens (38%), the caudate-putamen nucleus (62%) and the mesencephalon (320%), whereas adult D rats showed an increase of anandamide and 2-AG levels in the nucleus accumbens (50% and 24%, respectively) and of 2-AG in the caudate-putamen nucleus (48%), compared to adult AFR rats. Chronic administration of SR141716A to adolescent D rats blocked the escalation behavior in the morphine consumption test. Our data suggest that altered brain endocannabinoid levels may contribute to the escalation behavior in the morphine consumption test in a maternal deprivation model.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U952, Université Pierre et Marie Curie, 9 quai Saint Bernard, 75005 Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Naudon
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.forename: Bruno
authors.initials: B
authors.lastname: Giros
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Valérie
authors.initials: V
authors.lastname: Daugé
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D008297:Male; D008426:Maternal Deprivation; D009020:Morphine / Q000008:administration & dosage*; D009021:Morphine Dependence / Q000378:metabolism* / Q000523:psychology; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D063388:Endocannabinoids; D009020:Morphine