Naturally rewarding stimuli (i.e. food, sex, etc) increase the activity of dopamine cells in the mesocorticolimbic dopamine system causing increased dopamine release in brain areas such as the nucleus accumbens. Drugs of abuse mimic these effects, and hence, overexcite our brain’s natural reward system. Therefore, tempering drug-induced amplification of dopamine signaling is one approach to reduce the powerful effects of drugs on the brain. We have been exploring the potential of the neuromodulator, adenosine, to reduce excessive dopamine signaling that contributes to the development and persistence of psychostimulant abuse.

Dopamine’s effects in the brain are mediated by postsynaptic D1 and D2 receptors. Adenosine A1 and A2A receptors are uniquely positioned to counteract the excessive stimulation of dopamine receptors produced by drugs of abuse. Thus, adenosine receptor stimulation provides a “brake” on excessive dopamine receptor activity that ultimately influences drug-induced changes in neuronal function and behavior. My laboratory has been exploring three aspects of the role of adenosine-dopamine receptor interactions in psychostimulant abuse. First, we are interested in how psychostimulants such as cocaine and methamphetamine alter the expression of adenosine and dopamine receptors in the mesocorticolimbic dopamine system that may reduce adenosine receptor activity and favor excessive dopamine stimulation. Second, we are investigating how adenosine receptor stimulation impacts psychostimulant-induced behaviors (i.e. drug taking and relapse). Third, we are analyzing the mechanisms by which adenosine and dopamine receptors interact to influence psychostimulant-induced behaviors.