Effects of SKF-38393, a dopamine D1 receptor agonist on expression of amphetamine-induced behavioral sensitization and expression of immediate early gene arc in prefrontal cortex of rats.

Repeated administrations of psychostimulants into rodents produce behavioral sensitization. We examined whether a dopamine D1 agonist can reverse behavioral sensitization once established by repeated amphetamine (AMP) administrations and determined the mRNA expression levels of the D1 and D2 receptors, metabotropic glutamate receptor 1 (mGluR1), and activity-regulated cytoskeleton-associated protein (arc) in rats. Rats were pretreated with six intermittent AMP injections. Following a 14-day withdrawal period, the rats were divided into six groups and treated with either SKF-38393 (SKF; dopamine D1 agonist), SCH-23390 (SCH; selective D1 antagonist), YM-09151-2 (YM; selective D2 antagonist), SKF+SCH, SKF+YM or physiological saline once daily for 5 days. Three days or 4 weeks after the reversal treatments, all the rats were rechallenged with AMP. D1 and D2 antagonist treatments produced no significant decreases in locomotor activity or stereotyped behavior rate, respectively. In the SKF treatment group, stereotyped behavior rate decreased markedly after the three-day and four-week withdrawal periods. SKF+SCH treatment inhibited the effect of SKF treatment. The rats in the other groups that received AMP with or without SKF were decapitated 1 h after treatment, and the mRNA levels of the D1 and D2 receptors, mGluR1, and arc were measured by TaqMan real-time reverse transcriptase-polymerase chain reaction (RT-PCR). AMP administration significantly increased arc level. SKF also increased arc level significantly after the first single injection and after repeated injections of AMP during the pretreatment. There was no significant difference in arc expression level between the saline and SKF treatment groups after the AMP challenge, suggesting that arc expression level is not involved in the reversal effects of SKF in AMP sensitization.