Cardiovascular Changes Induced By Drugs of Abuse

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Research over the past year has continued to focus on the cardiovascular effects of adenosine receptor subtype agonists and antagonists in rats and of kappa receptor agonists in squirrel monkeys. 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 have 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. When CGS 21680 was injected into the NTS on a single side, no change in cardiovascular parameters were noted. It is likely that bilateral injections will be required to observed a cardiovascular effect. Kappa agonists have been proposed as treatments for psychostimulant abuse. Completed studies in squirrel monkeys implanted with arterial catheters have shown that kappa agonists produce large increases in heart rate. This is due to both the central effects of these drugs as shown in studies with ganglionic blockers and peripheral effects as a peripherally active kappa agonist also increases heart rate. The effects of the kappa agonists can be blocked by the opioid antagonist naltrexone, implicating the involvement of kappa opioid receptors. When given in combination with cocaine kappa agonists do not potentiate the effects of cocaine. Thus kappa agonists can be used safely in the treatment psychostimulant abuse.