Distinct roles of the endocannabinoids anandamide and 2-arachidonoylglycerol in social behavior and emotionality at different developmental ages in rats.
To date, our understanding of the relative contribution and potential overlapping roles of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the regulation of brain function and behavior is still limited. To address this issue, we investigated the effects of systemic administration of JZL195, that simultaneously increases AEA and 2-AG signaling by inhibiting their hydrolysis, in the regulation of socio-emotional behavior in adolescent and adult rats. JZL195, administered at the dose of 0.01mg/kg, increased social play behavior, that is the most characteristic social activity displayed by adolescent rats, and increased social interaction in adult animals. At both ages, these behavioral effects were antagonized by the CB1 cannabinoid receptor antagonist SR141716A and were associated with increased brain levels of 2-AG, but not AEA. Conversely, at the dose of 1mg/kg, JZL195 decreased general social exploration in adolescent rats without affecting social play behavior, and induced anxiogenic-like effects in the elevated plus-maze test both in adolescent and adult animals. These effects, mediated by activation of CB1 cannabinoid receptors, were paralleled by simultaneous increase in AEA and 2-AG levels in adolescent rats, and by an increase of only 2-AG levels in adult animals. These findings provide the first evidence for a role of 2-AG in social behavior, highlight the different contributions of AEA and 2-AG in the modulation of emotionality at different developmental ages and suggest that pharmacological inhibition of AEA and 2-AG hydrolysis is a useful approach to investigate the role of these endocannabinoids in neurobehavioral processes.
Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Rome, Italy.
Antonia
A
Manduca
Department of Physiology and Pharmacology, Sapienza, University of Rome, Rome, Italy; Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy and Psychiatry, University of Calgary, Calgary, AB, Canada.
Maria
M
Morena
Department of Physiology and Pharmacology, Sapienza, University of Rome, Rome, Italy.
Patrizia
P
Campolongo
Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Rome, Italy.
Michela
M
Servadio
Department of Physiology and Pharmacology, Sapienza, University of Rome, Rome, Italy.
Maura
M
Palmery
Department of Clinical and Experimental Medicine, Faculty of Medicine, University of Foggia, Foggia, Italy.
Luigia
L
Trabace
Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy and Psychiatry, University of Calgary, Calgary, AB, Canada.
Matthew N
MN
Hill
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Animals in Science and Society, Division of Behavioural Neuroscience, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Louk J M J
LJ
Vanderschuren
Department of Physiology and Pharmacology, Sapienza, University of Rome, Rome, Italy.
Vincenzo
V
Cuomo
Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Rome, Italy. Electronic address: viviana.trezza@uniroma3.it.
Viviana
V
Trezza
D000375:Aging / Q000187:drug effects / Q000378:metabolism / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D063388:Endocannabinoids / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005989:Glycerides / Q000378:metabolism*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D000077285:Rimonabant; D012919:Social Behavior
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002219:Carbamates; D063388:Endocannabinoids; D005989:Glycerides; C000592052:JZL195; D010879:Piperazines; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; C094503:glyceryl 2-arachidonate; D000077285:Rimonabant; C078814:anandamide
Emotional behavior; Endocannabinoid system; Endocannabinoids; JZL195; Rodents; Social behavior