Expression of amphetamine-induced behavioral sensitization after short- and long-term withdrawal periods: Participation of μ- and δ-opioid receptors

Abstract

Repeated amphetamine administration results in behavioralsensitization, an enduring behavioraltransformation expressed after short and long periods of withdrawal. To investigate the participation of the opioid system in amphetamine-induced behavioralsensitization, we studied the effect of naloxone, an opioid receptorantagonist, on the expression of behavioralsensitization tested after short- (2 days) and long-term (14 days) withdrawalperiods. In addition, using quantitative competitive RT-PCR, we examined the levels of m-opioid receptor (MOR) and d-opioid receptor (DOR) mRNA in the nucleus accumbensshell(NAcSh) and ventraltegmentalarea (VTA) of behaviorally sensitized rats, at these two withdrawaltimes. This study showed that whereas naloxone did not modify the expression of behavioralsensitization tested after 2 days of withdrawal, it completely blocked the expression when tested after 14 days of withdrawal. DOR and MOR mRNA levels were not modified in the NAcSh of rats expressing behavioralsensitization after 2 or 14 days of withdrawal. Conversely, DOR and MOR mRNA levels were elevated in the VTA of animals expressing behavioralsensitization after 2 days of withdrawal. However, whereas DOR mRNA returned to controllevels, MOR mRNA levels remained elevated in animals expressing behavioralsensitization after 14 days of withdrawal. These results indicate a striking difference between the role played by opioid receptors in the expression of amphetamine-induced behavioralsensitization, when tested after short- or long-term withdrawal periods. In addition, our results support the notion that repeated amphetamine-induced changes in opioid receptor expression may contribute to the perpetuation of psychostimulant abuse and/or relapse. © 2003 Nature Publishing Group.