The proposed project was designed to analyze individual differences in sensitivity to various effects of opioids with low to intermediate efficacy at the mu receptor. Using the drug discrimination and tail withdrawal assays, differences in sensitivity to the discriminative stimulus, rate-decreasing, and antiociceptive effects of these drugs will be examined in Experiment I. These differential sensitivities will be compared across assays within an individual animal in order to assess the degree of cross-sensitivity to these effects. Given these large interanimal differences, Experiment II will examine the degree of antagonism by naloxone, to determine whether these differences are due to interactions with separate populations of receptors across animals. Finally, the development of tolerance will be examined to see if differential magnitudes of tolerance become apparent across animals in Experiment III. The results of these studies will provide insight into the mechanisms by which individual differences in sensitivity to the effects of opioids are mediated and may help identify some of the environmental, genetic, and pharmacological influences which interact to produce these interanimal differences.
