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Reverse tolerance to amphetamine evokes reverse tolerance to 5-hydroxytryptophan
R Karler1, L D Calder, S A Turkanis
1Department of Pharmacology, University of Utah School of Medicine, Salt Lake City 84132.
Life Sciences
|January 1, 1990
Summary
Repeated amphetamine or 5-hydroxytryptophan (5-HTP) administration in mice induced reverse tolerance. These effects appear to be independent, mediated by dopaminergic mechanisms, suggesting distinct pathways for drug-induced neuroadaptation.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Amphetamine and 5-hydroxytryptophan (5-HTP) are key neurochemicals affecting behavior.
- Understanding drug-induced neuroplasticity, like reverse tolerance, is crucial for addiction research.
Purpose of the Study:
- To investigate the relationship between amphetamine and 5-HTP induced reverse tolerance.
- To determine the neurochemical mechanisms underlying these phenomena.
Main Methods:
- Repeated intermittent administration of amphetamine and 5-HTP in mice.
- Assessment of behavioral responses: head twitch (5-HTP) and stereotypy (amphetamine).
- Pharmacological interventions using haloperidol and cyproheptadine.
Main Results:
- Amphetamine administration induced reverse tolerance to both 5-HTP and amphetamine.
- 5-HTP administration alone also induced reverse tolerance to head twitch.
- Haloperidol blocked reverse tolerance to both drugs, while cyproheptadine selectively blocked 5-HTP reverse tolerance.
Conclusions:
- Amphetamine and 5-HTP induced reverse tolerance are independent events.
- Both phenomena are mediated by dopaminergic mechanisms.
- Distinct neurochemical pathways may underlie different forms of drug-induced neuroadaptation.