Extracellular Signal-Regulated Kinase in Nucleus Accumbens Mediates Propofol Self-Administration in Rats

Clinical and animal studies have indicated that propofol has potential for abuse, but the specific neurobi- ological mechanism underlying propofol reward is not fully understood. The purpose of this study was to inves- tigate the role of extracellular signal-regulated kinase （ERK） signal transduction pathways in the nucleus accumbens （NAc） in propofol self-administration. We tested the expression of p-ERK in the NAc following the maintenance of propofol self-administration in rats. We also assessed the effect of administration of SCH23390, an antagonist of the D1 dopamine receptor, on the expression of p-ERK in the NAc in propofol self-administering rats, and examined the effects of intra-NAc injection of U0126, an MEK inhibitor, on propofol reinforcement in rats. The results showed that the expression of p-ERK in the NAc increased significantly in rats maintained on propofol, and pre-treatment with SCH23390 inhibited the propofol self- administration and diminished the expression of p-ERK in the NAc. Moreover, intra-NAc injection of U0126 （4 μg/ side） attenuated the propofol self-administration. The data suggest that ERK signal transduction pathways coupledwith D1 dopamine receptors in the NAc may be involved in the maintenance of propofol self-administration and its rewarding effects.

Abstract Clinical and animal studies have indicated that propofol has potential for abuse, but the specific neurobi- ological mechanism underlying propofol reward is not fully understood. The purpose of this study was to inves- tigate the role of extracellular signal-regulated kinase （ERK） signal transduction pathways in the nucleus accumbens （NAc） in propofol self-administration. We tested the expression of p-ERK in the NAc following the maintenance of propofol self-administration in rats. We also assessed the effect of administration of SCH23390, an antagonist of the D1 dopamine receptor, on the expression of p-ERK in the NAc in propofol self-administering rats, and examined the effects of intra-NAc injection of U0126, an MEK inhibitor, on propofol reinforcement in rats. The results showed that the expression of p-ERK in the NAc increased significantly in rats maintained on propofol, and pre-treatment with SCH23390 inhibited the propofol self- administration and diminished the expression of p-ERK in the NAc. Moreover, intra-NAc injection of U0126 （4 μg/ side） attenuated the propofol self-administration. The data suggest that ERK signal transduction pathways coupledwith D1 dopamine receptors in the NAc may be involved in the maintenance of propofol self-administration and its rewarding effects.