title: Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to Delta9-tetrahydrocannabinol.
abstract: The present study evaluated the consequences of perinatal Delta(9)-tetrahydrocannabinol (Delta(9)-THC) treatment (5 mg/kg/day by gavage), either alone or combined with ethanol (3% v/v as the only fluid available), on ethanol self-administration and alcohol-seeking behavior in rat adult offspring. Furthermore, the effect of the selective cannabinoid CB(1) receptor antagonist, SR-141716A, on ethanol self-administration and on reinstatement of ethanol-seeking behavior induced either by stress or conditioned drug-paired cues was evaluated in adult offspring of rats exposed to the same perinatal treatment. Lastly, microarray experiments were conducted to evaluate if perinatal treatment with Delta(9)-tetrahydrocannabinol, ethanol or their combination causes long-term changes in brain gene expression profile in rats. The results of microarray data analysis showed that 139, 112 and 170 genes were differentially expressed in the EtOH, Delta(9)-THC, or EtOH+Delta(9)-THC group, respectively. No differences in alcohol self-administration and alcohol seeking were observed between rat groups. Intraperitoneal (IP) administration of SR-141716A (0.3-3.0 mg/kg) significantly reduced lever pressing for ethanol and blocked conditioned reinstatement of alcohol seeking. At the same doses SR-141716A failed to block foot-shock stress-induced reinstatement of alcohol seeking. The results reveal that perinatal exposure to Delta(9)-THC ethanol or their combination results in evident changes in gene expression patterns. However, these treatments do not significantly affect vulnerability to ethanol abuse in adult offspring. On the other hand, the results obtained with SR-141716A emphasize that endocannabinoid mechanisms play a major role in ethanol self-administration, as well as in the reinstatement of ethanol-seeking behavior induced by conditioned cues, supporting the idea that cannabinoid CB(1) receptor antagonists may represent interesting agents for the pharmacotherapy of alcoholism.
authors.affiliation: Department of Experimental Medicine and Public Health, University of Camerino, Via Scalzino 3, 62032 Camerino, Italy.
authors.forename: Daina
authors.initials: D
authors.lastname: Economidou
authors.forename: Laura
authors.initials: L
authors.lastname: Mattioli
authors.forename: Massimo
authors.initials: M
authors.lastname: Ubaldi
authors.forename: Anbarasu
authors.initials: A
authors.lastname: Lourdusamy
authors.forename: Laura
authors.initials: L
authors.lastname: Soverchia
authors.forename: Gary
authors.initials: G
authors.lastname: Hardiman
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cuomo
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccocioppo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D013759:Dronabinol / Q000633:toxicity*; D004359:Drug Therapy, Combination; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D020869:Gene Expression Profiling; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010880:Piperidines / Q000494:pharmacology*; D011247:Pregnancy; D011619:Psychotropic Drugs / Q000633:toxicity*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000077285:Rimonabant; D012646:Self Administration
chemical_list: D002492:Central Nervous System Depressants; D010880:Piperidines; D011619:Psychotropic Drugs; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000431:Ethanol; D013759:Dronabinol; D000077285:Rimonabant