title: Chronic co-administration of the cannabinoid receptor agonist WIN55,212-2 during puberty or adulthood reverses 3,4 methylenedioxymetamphetamine (MDMA)-induced deficits in recognition memory but not in effort-based decision making.
abstract: Cannabis and 3,4 methylenedioxymetamphetamine (MDMA, "ecstasy") are the most frequently combined illegal drugs among young adults in western societies. This study examined the effects of chronic co-administration of the cannabinoid receptor agonist WIN55,212-2 (WIN) and MDMA on working memory and effort-based decision making in rats. Treatment consisted of MDMA (7.5 mg/kg), WIN (1.2 mg/kg), a combination of these substances (MDMA+WIN) or vehicle over a period of 25 days during puberty (PD40-65) or adulthood (PD80-105). Ten days after the last treatment, WIN reversed MDMA-induced working memory deficits in the object recognition test in animals treated during adulthood or puberty, but had no influence on impairment of adult rats in the effort-based T-maze task. No differences were observed between groups of pubertally treated rats in the decision making task. During a subsequent acute drug challenge MDMA and MDMA+WIN decreased high reward choices in both age groups, indicating MDMA-induced cost-aversive choice. Differential long-term interactions on the neuronal level in the hippocampus and MDMA-induced disturbances in cortico-limbic connections are suggested.
authors.affiliation: Brain Research Institute, Department of Neuropharmacology, University of Bremen, 28359 Bremen, Germany. s.schulz@uni-bremen.de
authors.forename: Sybille
authors.initials: S
authors.lastname: Schulz
authors.forename: Thorsten
authors.initials: T
authors.lastname: Becker
authors.forename: Ulrich
authors.initials: U
authors.lastname: Nagel
authors.forename: Andreas
authors.initials: A
authors.lastname: von Ameln-Mayerhofer
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage* / Q000494:pharmacology; D003657:Decision Making / Q000187:drug effects*; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000187:drug effects*; D009025:Morpholines / Q000008:administration & dosage* / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009281:Naphthalenes / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation
chemical_list: D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D018817:N-Methyl-3,4-methylenedioxyamphetamine