title: Caffeine's Attenuation of Cocaine-Induced Dopamine Release by Inhibition of Adenosine.
abstract: Background:It is well known that the reinforcing properties of cocaine addiction are caused by the sharp increase of dopamine (DA) in the reward areas of the brain. However, other mechanisms have been speculated to contribute to the increase. Adenosine is one system that is associated with the sleep-wake cycle and is most important in regulating neuronal activity. Thus, more and more evidence is pointing to its involvement in regulating DA release. The current study set out to examine the role of adenosine in cocaine-induced DA release.Methods:Increasing doses of cocaine, caffeine, and their combination, as well as, 8-cyclopentyltheophylline (CPT), an adenosine A1 antagonist (alone and in combination with cocaine) were used to denote a response curve. A novel biosensor, the BRODERICK PROBE®was implanted in the nucleus accumbens to image the drug-induced surge of DA releasein vivo, in the freely moving animal in real time.Results:Combinations of cocaine and caffeine were observed to block the increased release of DA moderately after administration of the low dose (2.5 mg/kg cocaine and 12.5 mg/kg caffeine) and dramatically after administration of the high dose (10 mg/kg cocaine and 50 mg/kg caffeine), suggesting neuroprotection. Similarly, CPT and cocaine showed a decreased DA surge when administered in combination. Thus, the low and high dose of a nonselective adenosine antagonist, caffeine, and a moderate dose of a selective adenosine antagonist, CPT, protected against the cocaine-induced DA release.Conclusions:These results show a significant interaction between adenosine and DA release and suggest therapeutic options for cocaine addiction and disorders associated with DA dysfunction.
authors: Department of Physiology, Pharmacology and Neuroscience, The Sophie Davis School, The City College of New York , New York, New York. ; Department of Biology, CUNY Graduate Center , New York, New York. ; Center for Advanced Technology (CAT) CUNY , New York, New York.
authors: Lauren B
authors: LB
authors: Malave
authors: Department of Physiology, Pharmacology and Neuroscience, The Sophie Davis School, The City College of New York , New York, New York. ; Department of Biology, CUNY Graduate Center , New York, New York. ; Center for Advanced Technology (CAT) CUNY , New York, New York. ; Department of Neurology, NYU Langone Medical Center , New York, New York.
authors: Patricia A
authors: PA
authors: Broderick