Jeffery D. Steketee, Ph.D.
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Education:
Allegheny College, Meadville, PA, B.S., 1982, Biology/Psychology Research Interest:Our research group studies the neural mechanisms of drug addiction, with a particular focus on cocaine. The model that we use in our studies is behavioral sensitization. Sensitization has been proposed to underlie drug craving as well as the relapse to drug use following a period of abstinence. Behavioral sensitization is defined as the enhanced motor-stimulant response that occurs with repeated, intermittent exposure to drugs of abuse, such as cocaine. This behavioral response is generally paralleled by an enhancement of the cocaine-induced increase in dopamine overflow in the nucleus accumbens, as measured by in vivo microdialysis, which is considered neurochemical sensitization. Our laboratory uses both the behavioral and neurochemical measures to monitor the development of cocaine-induced sensitization. Recent studies in our lab have examined the potential role the medial prefrontal cortex (mPFC) plays in cocaine-induced sensitization. These studies have focused on cocaine-induced alterations in dopamine, GABA and glutamate transmission at both the neurotransmitter level and the receptor level. In the future these studies will be expanded to include behavioral models of reward and reinforcement. Another area of interest is studies on the potential “gateway” role solvent abuse may play in leading to the abuse of “harder” drugs. In our initial studies, we demonstrated that repeated exposure to toluene significantly increased the subsequent motor-stimulant response to cocaine in rats. This sensitized-like behavioral response to cocaine was paralleled by an augmented dopamine response to cocaine in the nucleus accumbens. These data suggest that repeated exposure to abused solvents can increase subsequent responses to cocaine. Ongoing studies using different behavioral models, such as self-administration and conditioned place preference, will determine whether solvent abuse indeed acts a gateway to future abuse of “harder” drugs. Neurochemical assays will also be conducted to understand the mechanisms by which solvent exposure alters subsequent behavioral responses to cocaine.
Selected Publications:
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