Research has focused 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. Rats are implanted with telemetry devices for recording blood pressure and heart rate. Various adenosine agonists and antagonists were then administered and blood pressure and heart rate were recorded for 1 hour. We have recently confirmed that the heart rate increasing effects of adenosine A2A agonists are mediated in the central nervous system while other effects of adenosine A2A and A1 agonists are mediated in the periphery. These experiments involved both peripheral and central administration of drug and pretreatment with ganglionic blockers. Currrent studies are focusing on the effects of adenosine agonists and antagonist following chronic caffeine treatment. Kappa agonists have been proposed as treatments for psychostimulant abuse. In squirrel monkeys implanted with arterial catheters kappa agonists produce large increases in heart rate. This is due to the central effects of these drugs as shown in studies with ganglionic blockers. When given in combination with cocaine kappa agonists do not potentiate the effects of cocaine, suggesting that kappa agonists can be used safely in the treatment psychostimulant abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000009-19
Application #
6987683
Study Section
(BNRB)
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
2004
Total Cost
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Schindler, Charles W; Graczyk, Zofi; Gilman, Joanne P et al. (2007) Effects of kappa opioid agonists alone and in combination with cocaine on heart rate and blood pressure in conscious squirrel monkeys. Eur J Pharmacol 576:107-13
Schindler, Charles W; Karcz-Kubicha, Marzena; Thorndike, Eric B et al. (2005) Role of central and peripheral adenosine receptors in the cardiovascular responses to intraperitoneal injections of adenosine A1 and A2A subtype receptor agonists. Br J Pharmacol 144:642-50
Schindler, Charles W; Karcz-Kubicha, Marzena; Thorndike, Eric B et al. (2004) Lack of adenosine A1 and dopamine D2 receptor-mediated modulation of the cardiovascular effects of the adenosine A2A receptor agonist CGS 21680. Eur J Pharmacol 484:269-75
Schindler, Charles W; Gilman, Joanne P; Graczyk, Zofi et al. (2003) Reduced cardiovascular effects of methamphetamine following treatment with selegiline. Drug Alcohol Depend 72:133-9
Schindler, C W; Gilman, J P; Bergman, J et al. (2002) Interactions between cocaine and dopamine agonists on cardiovascular function in squirrel monkeys. J Pharmacol Exp Ther 300:180-7
Schindler, C W; Zheng, J W; Goldberg, S R (2001) Effects of cocaine and cocaine metabolites on cardiovascular function in squirrel monkeys. Eur J Pharmacol 431:53-9
Tella, S R; Schindler, C W; Goldberg, S R (1999) Cardiovascular responses to cocaine self-administration: acute and chronic tolerance. Eur J Pharmacol 383:57-68
Erzouki, H K; Goldberg, S R; Schindler, C W (1999) Comparison of cocaine and Na+ channel blockers on cardio-respiratory function in the rabbit. Eur J Pharmacol 377:51-6
Itokawa, K; Sora, I; Schindler, C W et al. (1999) Heterozygous VMAT2 knockout mice display prolonged QT intervals: possible contributions to sudden death. Brain Res Mol Brain Res 71:354-7