Effects of physostigmine on the conditioned hyperactivity and locomotor sensitization to morphine in rats

Abstract

Repetitive exposure to opioids elicits sensitization to its psychomotor stimulating effect and environmental stimuli contribute to this effect. This study first developed a procedure that simultaneously measures conditioned hyperactivity and locomotor sensitization, and then investigated the effects of physostigmine on the development and expression of conditioned hyperactivity and locomotor sensitization in rats. Five groups of rats (10–12 rats each) were conditioned with a conditioned stimulus (CS) for 20min and then drug or saline paired with CS for 2h daily for 10 days. Rats were tested 20min on day 18. On day 25, rats were tested 20min and subsequently 2h (immediately after morphine injection). Although the 20min locomotion was not different among the rats on day 1, rats that received 5mg/kg morphine during conditioning showed higher locomotion than those received saline or 5mg/kg morphine in the home cage on day 18 and day 25. Rats received 0.1mg/kg physostigmine and 5mg/kg morphine during conditioning showed higher locomotion than those received 5mg/kg morphine on day 18. On day 25, 0.1mg/kg physostigmine attenuated the conditioned hyperactivity and expression of morphine locomotor sensitization. In contrast, rats received 0.1mg/kg physostigmine and 5mg/kg morphine during conditioning showed higher locomotion during 2h test period than those received 5mg/kg morphine. In conclusion, this study established a procedure that simultaneously study conditioned hyperactivity and locomotor sensitization. Physostigmine attenuates the expressions but enhances the development of conditioned hyperactivity and sensitization and the possible mechanisms are discussed.