The Roles of D1 and D2 dopamine receptors in mediating methamphetamine-induced changes in monoamine and substance P systems.

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Title The Roles of D1 and D2 dopamine receptors in mediating methamphetamine-induced changes in monoamine and substance P systems.
Publication Type dissertation
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Sonsalla, Patricia Kay
Contributor Lyon, Elaine
Date 1985-08
Description The amphetamine-like compounds have prominent effects on several neurotransmitter systems within the central nervous system. The administration of multiple doses of these stimulants produces profound and long-lasting decreases in neurochemical indices of dopamine and serotonergic systems as well as increases in the concentration of the neuropeptide, substance P, within various brain regions. The nonselective dopamine receptor antagonist, haloperidol, blocks these effects of methamphetamine on all three neurotransmitter systems. The purpose of the present investigations was to identify the dopamine receptor subtype(s) which mediate these actions of methamphetamine. Thus, selective D1 and D2 agonists and antagonists were administered alone or in combination with methamphetamine and the effects of these treatments on neurochemical parameters of the dopamine, serotonin, and substance P systems were evaluated. The results from these present studies suggest that methamphetamine-released dopamine actions on the D2 receptor mediate the effects of methamphetamine on the nigrostriatal dopamine and striatonigral substance P systems. In contrast, the effects of methamphetamine on serotonin systems appear to involve dopamine actions on the D1 receptor. A single administration of an amphetamine produces a rapid, but transient depression of serotonin synthesis. The coadministration of dopamine antagonists with methamphetamine did not modify the methamphetamine effect on tryptophan hydroxylase activity, the rate-limiting enzyme in serotonin synthesis. These findings suggest a different mechanism is involved in this acute, transient effect of methamphetamine versus the long-lasting effects observed after multiple administrations. Whereas D1 blockade attenuates the effects of methamphetamine on the serotonergic system in the multiple dosing paradigm, it does not afford protection against the acute effect.
Type Text
Publisher University of Utah
Subject Receptors; Dopamine
Subject MESH Drug Therapy; Methamphetamine; Substance P
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "The Roles of D1 and D2 dopamine receptors in mediating methamphetamine-induced changes in monoamine and substance P systems." Spencer S. Eccles Health Sciences Library. Print version of "The Roles of D1 and D2 dopamine receptors in mediating methamphetamine-induced changes in monoamine and substance P systems." available at J. Willard Marriott Library Special Collection. RM 31.5 1985 S65.
Rights Management © Patricia Kay Sonsalla.
Format application/pdf
Format Medium application/pdf
Identifier us-etd2,25337
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
ARK ark:/87278/s6fn1mpw
Setname ir_etd
ID 192360
Reference URL https://collections.lib.utah.edu/ark:/87278/s6fn1mpw
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