The role of the nucleus accumbens OXR1 in cocaine-induced locomotor sensitization

Abstract

Re-exposure to drug or drug-associated cues after withdrawal can induce behavioral sensitization expression in animals or increase in the expected effect to drug in humans, which mean an enhanced drug seeking/taking motivation to trigger relapse after abstinence. The Nucleus accumbens (NAc) is known to play a key role in mediating this motivation. Recently, it has been shown that systemic administration of orexin receptor 1 (OXR1) antagonist attenuates animals' motivation behavior to take drug by self-administration paradigm, which is more effectively than orexin receptor 2 (OXR2) antagonist. However, the effect of OXR1 in the NAc on drug-induced locomotor sensitization remains elusive. The present study was designed to investigate the effect of OXR1 in the NAc on chronic cocaine-induced locomotor sensitization. Rats were given 10 mg/kg cocaine intraperitoneal injection (i.p.) for five consecutive days, followed by 10 mg/kg cocaine re-exposure (challenge) on the 14th day of withdrawal. Results showed that re-exposure to cocaine after withdrawal could induce locomotor sensitization expression in cocaine-sensitized rats. Simultaneously, the number of OXR1 positive neurons and OXR1 membrane protein level in the NAc core but not the shell were significantly increased following the cocaine re-exposure. Further, micro-infusion of SB-334867, an OXR1 selective antagonist, into the NAc core but not the shell before cocaine re-exposure, significantly attenuated the expression of locomotor sensitization in rats. The findings demonstrate that OXR1 in the NAc core partially mediates the expression of chronic cocaine-induced locomotor sensitization.

Keywords: Cocaine; Locomotor sensitization; Nucleus accumbens; Orexin.