A prominent behavioral effect of opioids is their ability to influence both mood and motivation. Mu opioid receptor agonists produce euphoria in humans and function as positive reinforcers in a variety of species. Similar effects are observed in response to agonists at the delta receptor. In contrast, activation of the kappa opioid receptor is associated with aversive and dysphoric states. Although, increasing evidence has shown that it is such behavioral effects which are a critical factor in determining the abuse liability of psychoactive drugs, fundamental questions remain regarding the neural substrates mediating these effects. Similarly, an understanding of those factors, both endogenous and exogenous, which underlie individual differences in sensitivity to the motivational effects of opioids is lacking. It is these issues which are the subject of on-going research. Procedures which will enable analysis of the motivational properties of drug in rodents as well as their neurochemical basis are currently being developed. The conditioned place preference paradigm, which permits detection of both the reinforcing and aversive properties of drugs in experimental animals, has been set-up and control data obtained. This procedure will now be used to characterize the motivational effects of selective opioid receptor ligands as well as the neuroanatomical basis for such effects. An automated system for collection and analysis of conditioning data has been designed and is currently being refined. The technique of in-vivo microdialysis has now been established and conditions are being identified for high performance liquid chromatographic analysis of neurotransmitter release in discrete regions of the CNS. once such studies are completed, both microdialysis and conditioning studies will be conducted in parallel to permit a combined neurochemical/behavioral analysis of the mechanisms and factors leading to opioid addiction.
