Neuropeptide Y Y5 receptor antagonism causes faster extinction and attenuates reinstatement in cocaine-induced place preference

TY - JOUR

T1 - Neuropeptide Y Y5 receptor antagonism causes faster extinction and attenuates reinstatement in cocaine-induced place preference

AU - Sørensen, Gunnar

AU - Wörtwein, Gitta

AU - Fink-Jensen, Anders

AU - Woldbye, David P D

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2013/4

Y1 - 2013/4

N2 - Several studies have suggested a role for neuropeptide Y (NPY) in addiction to drugs of abuse, including cocaine. Recently, our group showed a role for the NPY Y5 receptor in the modulation of acute reinforcing effects of cocaine using self-administration and hyperlocomotion paradigms. In the present study, we further explored potential anti-addiction-related effects of Y5 antagonism in another murine model of cocaine addiction-related behavior: conditioned place-preference (CPP). Using this model, it was tested whether blockade or deficiency of the NPY Y5 receptor could influence the induction, extinction or reinstatement of a conditioned cocaine response. We found that the Y5 antagonist L-152,804 causes faster extinction and reduced reinstatement of cocaine-induced CPP but did not reduce the ability of cocaine to induce CPP. Similarly, Y5-KO mice displayed faster extinction, and reinstatement of cocaine-induced CPP was absent. The development of CPP for cocaine was similar between Y5-KO and WT mice. Taken together, the present data show that Y5 antagonism attenuates relapse to cocaine addiction-related behavior. Prevention of relapse is considered to be of pivotal importance for the development of an effective treatment against cocaine addiction and therefore Y5 receptors could be a potential future therapeutic target in cocaine addiction.

AB - Several studies have suggested a role for neuropeptide Y (NPY) in addiction to drugs of abuse, including cocaine. Recently, our group showed a role for the NPY Y5 receptor in the modulation of acute reinforcing effects of cocaine using self-administration and hyperlocomotion paradigms. In the present study, we further explored potential anti-addiction-related effects of Y5 antagonism in another murine model of cocaine addiction-related behavior: conditioned place-preference (CPP). Using this model, it was tested whether blockade or deficiency of the NPY Y5 receptor could influence the induction, extinction or reinstatement of a conditioned cocaine response. We found that the Y5 antagonist L-152,804 causes faster extinction and reduced reinstatement of cocaine-induced CPP but did not reduce the ability of cocaine to induce CPP. Similarly, Y5-KO mice displayed faster extinction, and reinstatement of cocaine-induced CPP was absent. The development of CPP for cocaine was similar between Y5-KO and WT mice. Taken together, the present data show that Y5 antagonism attenuates relapse to cocaine addiction-related behavior. Prevention of relapse is considered to be of pivotal importance for the development of an effective treatment against cocaine addiction and therefore Y5 receptors could be a potential future therapeutic target in cocaine addiction.

U2 - 10.1016/j.pbb.2013.02.010

DO - 10.1016/j.pbb.2013.02.010

M3 - Journal article

C2 - 23454535

SN - 0091-3057

VL - 105

SP - 151

EP - 156

JO - Pharmacology, Biochemistry and Behavior

JF - Pharmacology, Biochemistry and Behavior

ER -