Gnegy Lab

Amphetamine and its congeners, methamphetamine and cathinones (bath salts) are stimulant drugs that elicit euphoria, hyperactivity, tachycardia, appetite suppression and wakefulness in humans. In some individuals, repeated use of AMPH can lead to drug addiction and craving, along with anorexia, excessive heart stimulation and stroke. Amphetamines elicit these effects blocking uptake of catecholamines and by reversing plasmalemmal dopamine transporters (DAT) and norepinephrine transporters (NET), thus eliciting the release of the catecholamines into extracellular space.

The Gnegy laboratory explores the mechanism by which amphetamine interacts with its site of action in eliciting reinforcement, principally the dopamine transporter. We particularly focus on the role of signal transduction in altering amphetamine-induced reversal of the dopamine transporter. Our results demonstrate that the beta isozyme of protein kinase C (PKCb) enhances AMPH-stimulated reverse transport of dopamine and also diminishes dopamine autoreceptor activity. Both effects increase extracellular dopamine. Recently we have been exploring the action of PKC inhibitors in reducing amphetamine-stimulated locomotor and reinforcing behaviors. As a consequence of these activities, we are working to design and test drugs that would inhibit amphetamine-stimulated behaviors and reduce the reinforcing effects of amphetamine.