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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 II: DA, NE, and 5-HT mechanisms
W B West1, B J Van Groll, J B Appel
1Department of Psychology, University of South Carolina, Columbia 29208, USA.
Pharmacology, Biochemistry, and Behavior
|May 1, 1995
Summary
Dopamine systems are key to d-amphetamine effects, but norepinephrine and serotonin modulation is unclear. D1 antagonists blocked d-amphetamine cues, while other neurotransmitter antagonists/agonists showed no significant effects.
Area of Science:
- Neuropharmacology
- Behavioral Neuroscience
- Drug Discrimination
Background:
- Dopaminergic (DA) system activation is essential for d-amphetamine's behavioral effects.
- Norepinephrine (NE) and serotonin (5-HT) may modulate DA input, influencing subjective drug effects.
- Understanding these modulatory roles is crucial for characterizing d-amphetamine's complex actions.
Purpose of the Study:
- To investigate the roles of noradrenergic and serotonergic systems in mediating the stimulus effects of d-amphetamine.
- To determine if NE or 5-HT antagonists or agonists could mimic, block, or potentiate d-amphetamine's discriminative stimulus properties.
Main Methods:
- Rats were trained to discriminate d-amphetamine (1 mg/kg) from saline.
- Tests included combination (antagonism, potentiation) and substitution (generalization) with various DA, NE, and 5-HT agents.
- Specific antagonists (SCH 39166, prazosin, idazoxan, ketanserin, metergoline) and agonists/inhibitors (clonidine, salbutamol, nisoxetine, yohimbine, propranolol, ICS 205-930) were administered.
Main Results:
- The D1 antagonist SCH 39166 significantly blocked d-amphetamine's effects.
- NE and 5-HT antagonists did not alter the d-amphetamine cue.
- NE agonists, NE uptake inhibitors, and NE antagonists failed to mimic or block d-amphetamine effects; 5-HT3 antagonist ICS 205-930 potentiated low d-amphetamine doses, an effect blocked by prazosin.
Conclusions:
- Dopamine D1 receptor activation is critical for d-amphetamine's discriminative effects.
- Norepinephrine and serotonin systems do not appear to play a primary role in mediating the stimulus effects of d-amphetamine.
- A complex interaction exists between 5-HT3 receptors and NE alpha-1 receptors in modulating d-amphetamine's effects.
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