Interacting Cannabinoid and Opioid Receptors in the Nucleus Accumbens Core Control Adolescent Social Play.
Front. Behav. Neurosci.. 2016-11-16; 10:
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1. Front Behav Neurosci. 2016 Nov 16;10:211. eCollection 2016.
Interacting Cannabinoid and Opioid Receptors in the Nucleus Accumbens Core
Control Adolescent Social Play.
Manduca A(1), Lassalle O(1), Sepers M(1), Campolongo P(2), Cuomo V(2), Marsicano
G(3), Kieffer B(4), Vanderschuren LJ(5), Trezza V(6), Manzoni OJ(1).
(1)Institut National De La Santé Et De La Recherche Médicale U901Marseille,
France; Université de la Méditerranée UMR S901 Aix-Marseille 2Marseille, France;
(2)Department of Physiology and Pharmacology, Sapienza University of Rome Rome,
(3)NeuroCentre Magendie, Endocannabinoids and Neuroadaptation, Institut National
De La Santé Et De La Recherche Médicale U862Bordeaux, France; NeuroCentre
Magendie U862, University of BordeauxBordeaux, France.
(4)Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre
National de la Recherche Scientifique/Institut National de la Santé et de la
Recherche Médicale/Université de Strasbourg Illkirch, France.
(5)Division of Behavioural Neuroscience, Department of Animals in Science and
Society, Faculty of Veterinary Medicine, Utrecht University Utrecht, Netherlands.
(6)Section of Biomedical Sciences and Technologies, Department of Science,
University Roma Tre Rome, Italy.
Social play behavior is a highly rewarding, developmentally important form of
social interaction in young mammals. However, its neurobiological underpinnings
remain incompletely understood. Previous work has suggested that opioid and
endocannabinoid neurotransmission interact in the modulation of social play.
Therefore, we combined behavioral, pharmacological, electrophysiological, and
genetic approaches to elucidate the role of the endocannabinoid
2-arachidonoylglycerol (2-AG) in social play, and how cannabinoid and opioid
neurotransmission interact to control social behavior in adolescent rodents.
Systemic administration of the 2-AG hydrolysis inhibitor JZL184 or the opioid
receptor agonist morphine increased social play behavior in adolescent rats.
These effects were blocked by systemic pretreatment with either CB1 cannabinoid
receptor (CB1R) or mu-opioid receptor (MOR) antagonists. The social
play-enhancing effects of systemic morphine or JZL184 treatment were also
prevented by direct infusion of the CB1R antagonist SR141716 and the MOR
antagonist naloxone into the nucleus accumbens core (NAcC). Searching for
synaptic correlates of these effects in adolescent NAcC excitatory synapses, we
observed that CB1R antagonism blocked the effect of the MOR agonist DAMGO and,
conversely, that naloxone reduced the effect of a cannabinoid agonist. These
results were recapitulated in mice, and completely abolished in CB1R and MOR
knockout mice, suggesting that the functional interaction between CB1R and MOR in
the NAcC in the modulation of social behavior is widespread in rodents. The data
shed new light on the mechanism by which endocannabinoid lipids and opioid
peptides interact to orchestrate rodent socioemotional behaviors.