STRAIN DIFFERENCES IN THE REWARDING AND DOPAMINE-RELEASING EFFECTS OFMORPHINE IN RATS

Studies examining differential sensitivity to psychoactive drugs in mi ce suggest that genotype may play a critical role. Furthermore, an inv olvement of genotype in mediating individual differences in sensitivit y to the rewarding effects of several drugs of abuse has also been pos tulated. The aim of this study was to examine the conditioned rewardin g and dopamine-releasing effects of morphine in two outbred rat strain s commonly used in addiction research. Additionally, the behavioural a nd neuroendocrine responses of these strains to the stress of novelty were also examined. Basal locomotor activity was higher in Wistar rats than Sprague-Dawley following exposure to a novel environment. In con trast, elevations in plasma corticosteroid levels following novelty ex posure did not differ between the two strains. In a counterbalanced pl ace preference conditioning procedure, increasing doses of morphine (1 .0-10.0 mg/kg SC) produced significant conditioned place preferences ( CPP) in both Wistar and Sprague-Dawley strains. However, Wistar rats r equired a significantly larger dose of morphine (5.0 mg/kg) to produce a significant CPP than the Sprague-Dawley rats. In the latter strain, CPP occurred with doses of 3.0 mg/kg and greater. In parallel microdi alysis experiments, both strains showed significant dose-related incre ases in dopamine release in the nucleus accumbens following acute morp hine challenge (1.0-10.0 mg/kg SC). Again in Wistar rats, a larger dos e of morphine was necessary to produce a significant increase in compa rison to Sprague-Dawley rats. These results show that genetically dist inct rat strains can show differential sensitivity to opioids, more sp ecifically to drug-seeking responses.