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Stimulus effects of d-amphetamine 1: DA mechanisms.

B J Van Groll1, J B Appel

  • 1Department of Psychology, University of South Carolina, Columbia 29208.

Pharmacology, Biochemistry, and Behavior
|November 1, 1992
PubMed
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

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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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