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Orexin-1 receptor mediation of cocaine seeking in male and female rats

Academic Article
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Overview

authors

  • Zhou, L. Y.
  • Ghee, S. M.
  • Chan, C.
  • Lin, L.
  • Cameron, Michael
  • Kenny, Paul
  • See, R. E.

publication date

  • March 2012

journal

  • Journal of Pharmacology and Experimental Therapeutics  Journal

abstract

  • Previous studies have shown that female rats exhibit enhanced cocaine seeking during multiple phases of cocaine addiction compared with males. The orexin/hypocretin system recently has been implicated in drug addiction in male rats. Based on the known sex differences in cocaine addiction, in the current study we examined orexin-mediated cocaine seeking during self-administration, extinction, and reinstatement in age-matched male (initial weight 250-300 g) and female (initial weight 175-225 g) Sprague-Dawley rats by using the orexin-1 receptor (OX1R) antagonist 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl urea (SB-334867) (10-30 mg/kg). OX1R blockade had no effect on established cocaine self-administration, but attenuated cocaine seeking during extinction in both male and female rats. It is noteworthy that OX1R blockade potently attenuated cue-induced reinstatement in males but had no effect on females. SB-334867 also reduced cocaine seeking during pharmacological stress-induced (yohimbine, 2.5 mg/kg) and yohimbine + cue-induced reinstatement in both sexes. SB-334867 failed to affect reinstatement induced by cocaine (10 mg/kg) in either male or female rats, but selectively reduced cocaine + cue-induced reinstatement only in males. In separate experiments examining basal and cocaine-induced locomotion, SB-334867 attenuated locomotion in both male and female rats. Finally, assessment of plasma and brain levels of SB-334867 showed that estrus females had slightly higher plasma levels than diestrus females, but no overall sex differences or estrous cycle differences were observed in plasma or brain SB-334867 concentrations. These results show that OX1R signaling plays a role in mediating cocaine seeking, but differs between the sexes for cue-induced reinstatement.

subject areas

  • Animals
  • Benzoxazoles
  • Cocaine-Related Disorders
  • Cues
  • Extinction, Psychological
  • Female
  • Male
  • Motor Activity
  • Orexin Receptors
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Self Administration
  • Sex Characteristics
  • Urea
  • Yohimbine
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Identity

PubMed Central ID

  • PMC3286310

International Standard Serial Number (ISSN)

  • 0022-3565

Digital Object Identifier (DOI)

  • 10.1124/jpet.111.187567

PubMed ID

  • 22186370
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Additional Document Info

start page

  • 801

end page

  • 809

volume

  • 340

issue

  • 3

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