Rats will learn to lever-press when they are rewarded by amphetamine injections into the nucleus accumbens, morphine injections into the ventral tegmental area, or electrical stimulation of the lateral hypothalamus. These three powerful rewards have a number of common consequences in addition to their ability to establish and maintain lever-press habits; each of the three stimulates locomotor activity, each increases feeding, and the amphetamine and morphine injections potentiate brain stimulation reward and cause learned place-preferences. The working hypothesis of the proposed studies is that these several effects all result from activation of a common system in the brain, and that this system has, as one of its elements, the mesolimbic dopamine system which has long been associated with each of these behaviors. The experimental strategy is to attempt to dissociate the various behaviors and the various rewards on the basis of behavioral, electrophysiological, pharmacological, and neurochemical comparisons. Do the same parameters and loci of brain stimulation produce each of these behaviors? Do the same drugs influence each of the stimulation effects? Do the same receptor-selective opioids produce locomotion, feeding, and place-preference: establish lever-pressing habits; and facilitate brain stimulation reward? Are the same amphetamine isomers and dopamine agonists and the same sites of injection associated with amphetamine's ability to cause each of these behavioral effects? Finally, do each of these rewards activate the mesolimbic dopamine system--as directly measured by in vivo voltammetry and micodialysis assay procedures- -and do each of the challenges of each of the rewards alter their effects on the dopamine system? The answers to these questions are important for a full understanding of the neurobiology of addiction, and they bear on the validity of specific treatment procedures currently in use with human addicts.
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