Repeated orexin 1 receptor antagonism effects on cocaine seeking in rats

NEUROPHARMACOLOGY

卷:63

Article

Zhou, Luyi¹  Smith, Rachel J.¹  Do, Phong H.¹  Aston-Jones, Gary¹  See, Ronald E.¹ 

[1] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA

关键词: Cocaine;    Extinction;    Orexin;    Reinstatement;    SB-334867;    Self-administration;   

DOI  :  10.1016/j.neuropharm.2012.07.044

来源: Elsevier

【 摘 要 】

The orexin/hypocretin system has been implicated in multiple phases of drug addiction. Acute orexin receptor blockade with the orexin-1 receptor (OX1R) antagonist, SB-334867, has been found to reduce cocaine seeking after cocaine self-administration. As repeated drug dosing can have differential effects and is more clinically relevant than acute dosing, in the current study we examined the effects of repeated SB-334867 on cocaine self-administration, extinction, and reinstatement to cocaine seeking in Sprague Dawley rats. We found that repeated SB-334867 (10 mg/kg/day) had no effect on established cocaine self-administration. Repeated SB-334867 (both 10 and 20 mg/kg) attenuated cocaine seeking during extinction; however, this effect was only observed when animals had no prior experience with SB-334867 and when SB-334867 was administered prior to, but not after, daily extinction sessions. Notably, daily treatment with SB-334867 (10 mg/kg) during extinction increased subsequent cue-induced reinstatement, whereas repeated SB-334867 (20 mg/kg) administration during extinction enabled acute SB-334867 to reduce cue-induced reinstatement. Repeated SB-334867 treatment (10 or 20 mg/kg) failed to affect reinstatement induced by priming injections of cocaine (10 mg/kg). These results show that repeated inhibition of OX1R-mediated signaling exerts a lasting and specific role in mediating environmentally activated cocaine seeking. (c) 2012 Elsevier Ltd. All rights reserved.

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