Orexin-1 Receptor Mediation of Cocaine Seeking in Male and Female Rats
| Autor: | Ronald E. See, Shannon M. Ghee, Paul J. Kenny, Li Lin, Luyi Zhou, Clifford H. Chan, Michael D. Cameron |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Receptors Neuropeptide medicine.medical_specialty media_common.quotation_subject Self Administration Pharmacology Motor Activity Extinction Psychological Receptors G-Protein-Coupled Rats Sprague-Dawley Cocaine-Related Disorders Orexin Receptors Internal medicine medicine Animals Urea Naphthyridines media_common Estrous cycle Benzoxazoles Sex Characteristics Addiction Antagonist Yohimbine Orexin receptor Orexin Rats Endocrinology Behavioral Pharmacology Molecular Medicine Female Cues Self-administration Psychology medicine.drug Sex characteristics |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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