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Physiol Behav. 2016 Jul 1;161:140-144. doi: 10.1016/j.physbeh.2016.04.013. Epub 2016 Apr 9.

Central & peripheral glucagon-like peptide-1 receptor signaling differentially regulate addictive behaviors.

Author information

1
Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA. Electronic address: sunil.sirohi@wsu.edu.
2
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA.
3
Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
4
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA.

Abstract

Recent data implicate glucagon-like peptide-1 (GLP-1), a potent anorexigenic peptide released in response to nutrient intake, as a regulator for the reinforcing properties of food, alcohol and psychostimulants. While, both central and peripheral mechanisms mediate effects of GLP-1R signaling on food intake, the extent to which central or peripheral GLP-1R signaling regulates reinforcing properties of drugs of abuse is unknown. Here, we examined amphetamine reinforcement, alcohol intake and hedonic feeding following peripheral administration of EX-4 (a GLP-1 analog) in FLOX and GLP-1R KD(Nestin) (GLP-1R selectively ablated from the central nervous system) mice (n=13/group). First, the effect of EX-4 pretreatment on the expression of amphetamine-induced conditioned place preference (Amp-CPP) was examined in the FLOX and GLP-1R KD(Nestin) mice. Next, alcohol intake (10% v/v) was evaluated in FLOX and GLP-1R KD(Nestin) mice following saline or EX-4 injections. Finally, we assessed the effects of EX-4 pretreatment on hedonic feeding behavior. Results indicate that Amp-CPP was completely blocked in the FLOX mice, but not in the GLP-1R KD(Nestin) mice following EX-4 pretreatment. Ex-4 pretreatment selectively blocked alcohol consumption in the FLOX mice, but was ineffective in altering alcohol intake in the GLP-1R KD(Nestin) mice. Notably, hedonic feeding was partially blocked in the GLP-1R KD(Nestin) mice, whereas it was abolished in the FLOX mice. The present study provides critical insights regarding the nature by which GLP-1 signaling controls reinforced behaviors and underscores the importance of both peripheral and central GLP-1R signaling for the regulation of addictive disorders.

KEYWORDS:

Alcohol intake; Amphetamine reinforcement; GLP-1; GLP-1R; Hedonic feeding

PMID:
27072507
DOI:
10.1016/j.physbeh.2016.04.013
[Indexed for MEDLINE]

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