TrkB signaling is required for behavioral sensitization and conditioned place preference induced by a single injection of cocaine

NEUROPHARMACOLOGY

卷:58

Article

Crooks, Kristy R.²  Kleven, Daniel T.²  Rodriguiz, Ramona M.¹  Wetsel, William C.^1,2,3,4  McNamara, James O.^5,6 

[1] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Mouse Behav & Neuroendocrine Anal Core Facil, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA

[3] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA

[4] Duke Univ, Med Ctr, Dept Med Endocrinol, Durham, NC 27710 USA

[5] Duke Univ, Med Ctr, Dept Neurol, Durham, NC 27710 USA

[6] Duke Univ, Med Ctr, Dept Pharmacol & Mol Canc Biol, Durham, NC 27710 USA

关键词: Transgenic mice;    TrkB receptor;    Brain-derived neurotrophic factor;    Cocaine;    Behavioral sensitization;    Conditioned place preference;   

DOI  :  10.1016/j.neuropharm.2010.01.014

来源: Elsevier

【 摘 要 】

Exogenous brain-derived neurotrophic factor (BDNF) can regulate behavioral sensitization and conditioned place preference (CPP) when animals are exposed to repeated cocaine administration. However, it is unclear whether BDNF signaling through the TrkB receptor can mediate these behavioral responses when animals are given a single cocaine exposure. Because TrkB knockout mice die as neonates, we engineered a transgenic mouse that expressed a dominant negative form of TrkB (dnTrkB) in a conditional and reversible manner. We assessed also activation of endogenous TrkB by quantifying levels of phosphorylated TrkB (p-TrkB) in the nucleus accumbens (NAc). We found that a single exposure to cocaine was sufficient to increase p-TrkB within the NAc 9-12 h after administration. Expression of the dnTrkB transgene not only prevented the acute cocaine-induced increase in p-TrkB, but it also prevented behavioral sensitization and CPP following a single cocaine injection. These findings demonstrate that TrkB activation is required both for behavioral sensitization and CPP to a single cocaine exposure. The fact that enhanced TrkB activation is induced within 9 h of a single injection of cocaine suggests that inhibition of TrkB signaling commencing hours after cocaine exposure may prevent at least the initial antecedents to the sensitizing and reinforcing effects of this psychostimulant. (C) 2010 Published by Elsevier Ltd.

【 授权许可】

Free