The long-term goal of this research is a better understanding of neurobehavioral factors determining the addictive liabilities of drugs (stimulants and opiates). A major focus is the determination of neuroanatomical site(s) and mode(s) of drug action(s) with particular reference to differential involvement of the two sides of the brain. The methodology uses rats and involves relating a behavioral index (rotation or circling behavior) of asymmetry motor activity and brain chemistry. Neurochemical effect of drugs and neurochemical correlates of behavior are determined by using in vivo microdialysis to obtain prefusates of discrete brain regions; extracellular levels of biogenic amines (dopamine, norepinephrine, serotonin) and their metabolites are then measured by HPLC. Specific experimental problems include the following: (1) Mechanisms that characterize and differentiate drug classes (i.e., opiates vs. stimulants) as well as different drugs of the same class (e.g., cocaine vs. d- amphetamine) will continue to be investigated with respect to their bilateral effects on dopamine release in several brain regions; the effects of repeated drug administration, with respect to mechanisms of sensitization and tolerance, will also be studied. (2) Relationship of individual differences in brain lateralization to behavioral differences in sensitivity to opiates (e.g., morphine, meperidine) and stimulants (e.g., d-amphetamine, cocaine) will be further characterized; the hypothesis that changes in drug responsiveness will occur as a result of altering temporal relationship between drug self-administration and dopamine release in brain will be directly analyzed using in vivo microdialysis; an important goal will be to distinguish which neurochemical events precede or elicit drug seeking behavior and which neurochemical events are the result or consequence of drug intake. These studies should provide basic information on mechanisms of drug actions as well as an animal model for understanding interindividual differences in drug preferences and patterns of abuse among humans.
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