title: Endocannabinoids in amygdala and nucleus accumbens mediate social play reward in adolescent rats.
abstract: The brain endocannabinoid system plays a crucial role in emotional processes. We have previously identified an important role for endocannabinoids in social play behavior, a highly rewarding form of social interaction in adolescent rats. Here, we tested the hypothesis that endocannabinoid modulation of social play behavior occurs in brain regions implicated in emotion and motivation. Social play increased levels of the endocannabinoid anandamide in the amygdala and nucleus accumbens (NAc), but not in prefrontal cortex or hippocampus of 4- to 5-week-old male Wistar rats. Furthermore, social play increased phosphorylation of CB1 cannabinoid receptors in the amygdala. Systemic administration of the anandamide hydrolysis inhibitor URB597 increased social play behavior, and augmented the associated elevation in anandamide levels in the amygdala, but not the NAc. Infusion of URB597 into the basolateral amygdala (BLA) increased social play behavior, and blockade of BLA CB1 cannabinoid receptors with the antagonist/inverse agonist SR141716A prevented the play-enhancing effects of systemic administration of URB597. Infusion of URB597 into the NAc also increased social play, but blockade of NAc CB1 cannabinoid receptors did not antagonize the play-enhancing effects of systemic URB597 treatment. Last, SR141716A did not affect social play after infusion into the core and shell subregions of the NAc, while it reduced social play when infused into the BLA. These data show that increased anandamide signaling in the amygdala and NAc augments social play, and identify the BLA as a prominent site of action for endocannabinoids to modulate the rewarding properties of social interactions in adolescent rats.
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands. vtrezza@uniroma3.it
authors.forename: Viviana
authors.initials: V
authors.lastname: Trezza
authors.forename: Ruth
authors.initials: R
authors.lastname: Damsteegt
authors.forename: Antonia
authors.initials: A
authors.lastname: Manduca
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Linda W M
authors.initials: LW
authors.lastname: Van Kerkhof
authors.forename: R Jeroen
authors.initials: RJ
authors.lastname: Pasterkamp
authors.forename: Yeping
authors.initials: Y
authors.lastname: Zhou
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cuomo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Louk J M J
authors.initials: LJ
authors.lastname: Vanderschuren
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001549:Benzamides / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007398:Interpersonal Relations; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D010988:Play and Playthings; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D012201:Reward; D000077285:Rimonabant; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001549:Benzamides; D063386:Cannabinoid Receptor Agonists; D002219:Carbamates; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D010739:Phospholipase D; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C527163:Napepld protein, rat