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Presynaptic Dopamine Dynamics in Striatal Brain Slices with Fast-scan Cyclic Voltammetry
Published on: January 12, 2012
Interactions between cocaine and dopamine agonists on cardiovascular function in squirrel monkeys.
C W Schindler1, J P Gilman, J Bergman
1Preclinical Pharmacology Section, Behavioral Neuroscience Branch, National Institutes of Health/National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland 21224, USA. cschindl@helix.nih.gov
The Journal of Pharmacology and Experimental Therapeutics
|December 26, 2001
Summary
Cocaine and dopamine D1 agonists, like SKF 82958, increase blood pressure and heart rate in monkeys. While D1 agonists and uptake inhibitors appear safe with cocaine, dopamine autoreceptor antagonists require caution.
Area of Science:
- Pharmacology
- Neuroscience
Background:
- Cocaine abuse is a significant public health issue.
- Dopamine agonists are being explored as potential treatments for cocaine abuse.
- Understanding the cardiovascular effects of dopamine agonists and their interactions with cocaine is crucial.
Purpose of the Study:
- To investigate the cardiovascular effects of various dopamine receptor agonists and a dopamine uptake inhibitor in conscious squirrel monkeys.
- To determine the interaction effects of these drugs when co-administered with cocaine.
- To assess the potential safety of combining dopamine agonists with cocaine for therapeutic purposes.
Main Methods:
- Conscious squirrel monkeys were administered cocaine and various dopamine agonists (D1 and D2) and a dopamine uptake inhibitor intravenously.
- Cardiovascular parameters including blood pressure, heart rate, and rate-pressure product (RPP) were monitored.
- Drug interactions were assessed by co-administering compounds with cocaine.
Main Results:
- Cocaine, the D1 agonist SKF 82958, and the dopamine uptake inhibitor GBR 12909 dose-dependently increased blood pressure, heart rate, and RPP.
- The D1 agonist SKF 81297 was less potent, and the partial D1 agonist SKF 77434 had minimal effects.
- Combinations of cocaine with D1 agonists or GBR 12909 showed subadditive effects, while the dopamine autoreceptor antagonist UH 232 demonstrated additive effects.
- The D2 agonist quinpirole had minimal cardiovascular effects and additive heart rate effects with cocaine.
Conclusions:
- Dopamine D1 agonists and dopamine uptake inhibitors may be safely combined with cocaine regarding cardiovascular effects.
- Dopamine autoreceptor antagonists, like UH 232, may produce additive cardiovascular effects with cocaine, warranting caution.
- These findings inform the potential therapeutic use of dopamine-targeting drugs in cocaine abuse treatment.
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