Cardiovascular Changes Induced By Drugs of Abuse

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Adenosine plays a role in the behavioral effects of caffeine, one of the most widely used drugs in the world. We have previously shown that adenosine A2A agonists can increase heart rate in rats, an effect that appears to be medicated by CNS adenosine receptors. The site of action for this effect has been hypothesized to be the nucleus tractus solitarius (NTS). To investigate this possibility further, we previously implanted microdialysis probes in the NTS and administered the adenosine agonist CGS 21680. CGS 21680 produced an increase in the level of glutamate in the NTS, while the adenosine A2A antagonist MSX-3 produced a decrease of glutatmate, suggesting a tonic level of control by adenosine. The combination of CGS 21680 and MSX-3 produced no change in glutatmate. We are currently investigating whether the injection of CGS 21680 into the NTS will produce cardiovascular effects similar to systemic administration in an effort to confirm that the NTS regulates these effects of adenosine agonists.