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Single Cell Measurement of Dopamine Release with Simultaneous Voltage-clamp and Amperometry
Published on: November 21, 2012
Stimulus effects of d-amphetamine 1: DA mechanisms
1Department of Psychology, University of South Carolina, Columbia 29208.
Pharmacology, Biochemistry, and Behavior
|November 1, 1992
Summary
Dopamine uptake inhibition by GBR 12909 mimics d-amphetamine effects in rats. Direct dopamine receptor stimulation is insufficient, and D1 receptor blockade significantly reduces amphetamine
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Monoaminergic systems are crucial for the subjective effects of CNS stimulants.
- Understanding dopamine's role is key to characterizing stimulant action.
Purpose of the Study:
- To investigate the role of dopaminergic mechanisms in the discriminative effects of d-amphetamine.
- To determine if dopamine uptake inhibition or direct receptor stimulation mediates amphetamine's subjective effects.
Main Methods:
- Rats were trained to discriminate d-amphetamine from saline.
- Substitution tests were conducted using a dopamine (DA) uptake inhibitor (GBR 12909) and D1/D2 agonists (SK&F 38393, quinpirole).
- Antagonists (SCH 23390, metoclopramide) were used in combination with d-amphetamine to assess receptor blockade effects.
Main Results:
- The dopamine uptake inhibitor GBR 12909 fully mimicked d-amphetamine's effects at 20 mg/kg.
- Neither D1 nor D2 agonists produced d-amphetamine-like responding.
- D1 antagonist SCH 23390 blocked the d-amphetamine cue, while the D2 antagonist metoclopramide did not.
Conclusions:
- Dopamine uptake inhibition contributes significantly to the discriminative effects of d-amphetamine.
- Direct stimulation of D1 or D2 receptors alone is insufficient to replicate d-amphetamine's subjective effects.
- D1 receptor blockade attenuates d-amphetamine's effects more than D2 receptor blockade.
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