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The Journal of Neuroscience, September 24, 2008, 28(39):9702-9709; doi:10.1523/JNEUROSCI.1171-08.2008

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Behavioral/Systems/Cognitive
Activating Parabrachial Cannabinoid CB₁ Receptors Selectively Stimulates Feeding of Palatable Foods in Rats

Nicholas V. DiPatrizio and Kenny J. Simansky

Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102

Correspondence should be addressed to Kenny J. Simansky, Drexel University College of Medicine, Department of Pharmacology and Physiology, 245 North 15th Street, MS #488, Philadelphia, PA 19102. Email: ksimansk{at}drexelmed.edu

The endocannabinoid system is emerging as an integral component in central and peripheral regulation of feeding and energy balance. Our investigation analyzed behavioral roles for cannabinoid mechanisms of the pontine parabrachial nucleus (PBN) in modulating intake of presumably palatable foods containing fat and/or sugar. The PBN serves to gate neurotransmission associated with, but not limited to, the gustatory properties of food. Immunofluorescence and in vitro [³⁵S]GTPS autoradiography of rat tissue sections containing the PBN revealed the presence of cannabinoid receptors and their functional capability to couple to their G-proteins after incubation with the endocannabinoid 2-arachidonoyl glycerol (2-AG). The selective cannabinoid 1 receptor (CB₁R) antagonist AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] prevented the response, demonstrating CB₁R mediation of 2-AG-induced coupling. Microinfusions of 2-AG into the PBN in behaving rats robustly stimulated feeding of pellets high in content of fat and sucrose (HFS), pure sucrose, and pure fat (Crisco), during the first 30 min after infusion. In contrast, 2-AG failed to increase consumption of standard chow, even when the feeding regimen was manipulated to match baseline intakes of HFS. Orexigenic responses to 2-AG were attenuated by AM251, again indicating CB₁R mediation of 2-AG actions. Furthermore, responses were regionally specific, because 2-AG failed to alter intake when infused into sites 500 µm caudal to infusions that successfully stimulated feeding. Our data suggest that hedonically positive sensory properties of food enable endocannabinoids at PBN CB₁Rs to initiate increases in eating, and, more generally, these pathways may serve a larger role in brain functions controlling behavioral responses for natural reward.

Key words: brainstem; cannabinoids; CB₁ receptor; eating; feeding; opioid; parabrachial; reward

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Received March 18, 2008; revised July 11, 2008; accepted Aug. 17, 2008.

Correspondence should be addressed to Kenny J. Simansky, Drexel University College of Medicine, Department of Pharmacology and Physiology, 245 North 15th Street, MS #488, Philadelphia, PA 19102. Email: ksimansk{at}drexelmed.edu

This article has been cited by other articles:

				A. D. de Kloet and S. C. Woods Endocannabinoids and Their Receptors as Targets for Obesity Therapy Endocrinology, June 1, 2009; 150(6): 2531 - 2536. [Abstract] [Full Text] [PDF]

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