The long-term objective is to determine the behavioral correlates of the ethanol action which accounts for ethanol's reinforcing property (and thus its abuse liability). It is hypothesized that the psychomotor stimulant properties of drugs of abuse represent such a correlate. The goal of the proposed studies is to more fully characterize the psychomotor stimulant properties of ethanol, with particular references to paradigms which appear to reflect reinforcement correlates.
The specific aims are to study ethanol in three such paradigms: (i) the brain stimulation reward paradigm, (ii) stimulation-induced and deprivation-induced feeding paradigms, and (iii) the unilateral dopamine lesion rotation paradigm. In each case, stimulant effects will be expected. Work with the first paradigm will focus on methods to demonstrate more robust facilitation of brain stimulation reward: a more powerful paradigm than has been used in the past will be used; the role of dose, route of administration, stimulation parameters, and site of stimulation will be systematically explored. Effects of ethanol on feeding will be examined within stimulation-induced and deprivation induced meals. Facilitation of feeding is expected from the working hypothesis, and sensitive measures will be used to look for such effects. The rotation paradigm will be used to explore the effects of ethanol on locomotion; drugs known to cause locomotion by activating the dopamine pathway involved in reinforcement cause circling when injected into animals with unilateral dopamine depletions. The work has direct relevance to the understanding of the neurobiology of alcoholism. Ethanol has actions in several brain regions, and the mechanisms of the various actions are not well understood. Theory in physiological psychology suggests that the same brain mechanism plays a role in psychomotor stimulant and reinforcing actions; the proposed studies explore this possibility. Inasmuch as reinforcing effects of pharmacological doses of ethanol are difficult to demonstrate in laboratory animals, unconditioned psychomotor stimulant effects--which are more readily demonstrated--may offer a more useful behavioral and end-point for laboratory studies of the interaction of ethanol with reinforcement-related brain circuitry.
