Repeated pre-exposure to morphine into the ventral pallidum enhances morphine-induced place preference: involvement of dopaminergic and opioidergic mechanisms.

In the present study, the effect of repeated administration of morphine into the ventral pallidum (intra-VP) on the conditioned place preference (CPP) induced by systemic morphine injection was investigated in male Wistar rats. Subcutaneous (s.c.) administration of morphine (2.5, 5 and 7.5mg/kg), during conditioning, induced conditioned place preference (CPP). The maximum response was obtained with 5mg/kg of morphine. Lower dose of morphine (0.5mg/kg) did not induce CPP, but in the animals which had previously, received 3 days intra-VP repeated injections of morphine (3 or 5microg/rat) followed by 5 days free of the drug, elicited a significant CPP. Moreover, 3 days intraperitoneal (i.p.) pretreatment with different doses of naloxone (0.5, 1 and 2mg/kg), SCH 23390 (0.012, 0.025 and 0.05mg/kg) or sulpiride (6.2, 12.5 and 25mg/kg) in combination with repeated injections of morphine (5microg/rat), blocked the opioid response on the acquisition of morphine (0.5mg/kg) CPP. On the other hand, our results showed that 3 days single repeated administration of different doses of naloxone (0.5, 1 or 2mg/kg, i.p.), SCH 23390 but not sulpiride followed by 5 days free of the drug, significantly decreased the acquisition of morphine (0.5mg/kg) CPP and also induced place aversion. Furthermore, the drugs' injections had no effect on locomotor activity on the testing phase of CPP. It is concluded that repeated intra-VP injections of morphine induces behavioral sensitization, which may be due to the opioidrgic and/or dopaminergic mechanism(s).