The long-term goal of this research is a better understanding of what factors determine the addictive liabilities of drugs. Using prototypical agents, experiments are planned to analyze further the neuropsychological mechanisms of opiate (e.g., morphine, meperidine), stimulant (e.g., d-amphetamine, cocaine), and hallucinogen (e.g., phencyclidine, LSD) addiction in rats. A major focus will be the determination of neuroanatomical site(s) of drug action(s) with particular reference to differential involvement of the two sides of the brain. Specific experimental problems will include the following: (1) The effects of drugs on electrical self-stimulation of the brain will continue to be studied and characterized in terms of their differential actions in the two sides of the brain. Ongoing studies with lateral hypothalamic and hippocampal placements will be completed, and striatum and frontal cortex will be studied next. (2) Mechanisms that differentiate cocaine from d-amphetamine will be investigated with respect to the hypothesis that cocaine selectively activates dopaminergic mesocortical pathways that can also be activated by stress. (3) The mechanism of asymmetry in the dopaminergic nigrostriatal system will be investigated with respect to the hypothesis that there are dual excitatory and inhibitory inputs and that rats can be distinguished on the basis of which input predominates. (4) Individual differences in brain lateralization that underlie behavioral differences in sensitivity to opiates, stimulants, and hallucinogens will be investigated. Left-, right- and non-sided rats of both sexes will be compared for their responsiveness to behavioral effects (e.g., drug self-administration, locomotor activity) of these drugs. If possible, similar comparisons will be made between rats distinguished as in (3) above. These studies should provide an animal model for understanding different drug preferences and patterns of abuse among humans.
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