Abstract: Behavioral sensitization is defined as an increased behavioral response after repeated intermittent treatment with various drugs of abuse and is thought to be involved in drug abuse and addiction. This experiment examined the effects of Huperzine A on stress-induced expression of morphine behavioral sensitization in rats. Rats were treated with saline or morphine (3 mg/kg) for 7 days to induce behavioral sensitization (defined as a progressive increase of locomotor activity in the current study). In the subsequent experimental sessions, a stressor (empty bottle during scheduled water availability) was introduced acutely or chronically to elicit expression of morphine sensitization. The locomotor activities of the rats were monitored daily by using computer-interfaced monitoring system. The distance traveled (cm) during the development period was analyzed by two-way ANOVA with treatment day as the repeated measure. The data from the two challenge tests were separately analyzed by one-way ANOVA. Post hoc analyses (LSD test) were performed for assessing specific group comparison. Morphine induced significant behavioral sensitization during daily treatment. Environmental cue elicited marked hyperactivity during morphine discontinuation, which gradually dissipated within 7 days. Acute or chronic stress treatment both markedly induced expression of behavioral sensitization. A challenge dose of morphine markedly elicited the expression of behavioral sensitization, which was prevented by Huperzine A. In conclusion, this study demonstrated that stress induces robust expression of morphine sensitization and this can be inhibited by a cholinesterase inhibitor Huperzine A. This suggests that drugs that act as cholinesterase inhibitors (e.g. Huperzine A) may be useful therapeutics for opioid addiction.

Key words: Huperzine A, behavioral sensitization, morphine, stress