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Increased dopamine release by the autoreceptor antagonist (+)-AJ 76 is Ca2(+)-dependent
N Waters1, L Löfberg, K Svensson
1Department of Pharmacology, University of Göteberg, Sweden.
European Journal of Pharmacology
|October 23, 1990
Summary
(+)-AJ 76, a dopamine autoreceptor antagonist, increases dopamine release and metabolism. This release is calcium-dependent and originates from vesicles, unlike d-amphetamine.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Dopamine plays a crucial role in neurotransmission, influencing mood, reward, and motor control.
- Autoreceptors modulate neurotransmitter release, offering potential therapeutic targets.
Purpose of the Study:
- To investigate the effects of (+)-AJ 76, a selective dopamine autoreceptor antagonist, on dopamine release and metabolism.
- To compare the calcium (Ca2+) dependence of (+)-AJ 76 and d-amphetamine on dopamine dynamics.
- To elucidate the origin and regulation of dopamine release induced by (+)-AJ 76.
Main Methods:
- In vivo brain microdialysis in a rodent model.
- Administration of (+)-AJ 76 and d-amphetamine.
- Measurement of extracellular dopamine levels and metabolites.
- Manipulation of extracellular Ca2+ concentrations.
Main Results:
- (+)-AJ 76 significantly increased dopamine release and metabolism.
- Dopamine release induced by (+)-AJ 76 was saturable and Ca2+-dependent.
- Metabolism of dopamine by (+)-AJ 76 was independent of extracellular Ca2+.
- Dopamine release and metabolism by d-amphetamine were independent of both Ca2+ and neuronal impulse flow.
- (+)-AJ 76-induced dopamine release was dependent on neuronal impulse flow and of vesicular origin.
Conclusions:
- (+)-AJ 76 releases dopamine via a mechanism dependent on neuronal activity and vesicular stores.
- The mechanisms underlying dopamine release and metabolism by (+)-AJ 76 may differ.
- (+)-AJ 76 and d-amphetamine likely release dopamine from distinct neuronal pools, suggesting different pharmacological profiles.