The aim of the proposed work is to compare the behavioral effects of cocaine and procaine in rats. The significance of the work lies in what appears to be a fundamental inconsistency regarding the proposed mechanism by which cocaine exerts central effects. Cocaine has very high abuse potential and its primary reinforcing property, like that of other stimulants, has been attributed to its effects on central dopaminergic systems. Despite no demonstrated dopaminergic activity comparable to that of cocaine, procaine also self-administered by non-human primates. The two compounds also exhibit similar stimulus properties in rodents as determined in drug discrimination tests, despite the fact that procaine does not share the (presumably dopamine mediated) locomotor stimulant properties od cocaine. procaine thus has primary reinforcing and stimulus properties like those of cocaine without demonstrated effect of the dopaminergic system(s) through which cocaine ostensibly manifests these properties. The experiments proposed herein compare cocaine and procaine with the objective of understanding the mechanism(s) through which they operate to achieve similar properties while apparently not sharing dopamine agonist activity. Three behavioral procedures will be utilized: rotational behavior, drug discrimination and self-administration. In the rotational behavior paradigm, unilaterally 6-hydroxydopamine lesioned rats will be tested for rotational (circling) behavior after acute cocaine treatment and acute and chronic procaine treatment. Behavior in this paradigm is extraordinarily sensitive to dopamine agonists and should reveal any heretofore undemonstrated dopaminergic effects of procaine. In the drug discrimination paradigm rats will be trained to discriminate cocaine or procaine from saline and the stimulus properties of each will be characterized by the use of generalization and antagonism tests. In the self-administration paradigm, the ability of procaine to serve as a primary reinforcer in otherwise drug-naive rets will be tested. If procaine is self- administered by naive rats it should prove a useful model for further elucidation of the cocaine-like properties of procaine and other local anesthetics.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
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Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
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University of Texas Health Science Center Houston
Schools of Medicine
United States
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Silverman, P B (1990) Cocaine and local anesthetics: stimulant activity in rats with nigral lesions. Psychopharmacology (Berl) 102:269-72
Silverman, P B (1990) Direct dopamine agonist-like activity conditioned to cocaine. Pharmacol Biochem Behav 37:231-4
Silverman, P B; Baruch, N P; Schultz, K A (1989) One trial conditioning with apomorphine is blocked by cycloheximide. Pharmacol Biochem Behav 34:663-4
Silverman, P B (1989) One-trial conditioned rotation in rats. NIDA Res Monogr 95:540-1
Silverman, P B (1988) Apomorphine induces latent rotation in lesioned rats, amphetamine does not. Life Sci 42:2397-401