Document Detail


Evidence that serotonin mediates some behavioral effects of amphetamine.
MedLine Citation:
PMID:  308099     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the rat, d-amphetamine sulfate (15--80 mg/kg) causes numerous behavioral effects including simultaneous side-to-side head weaving or head tremor, forepaw padding and splayed hindlimbs. These signs are strikingly similar to a behavioral syndrome caused by intense serotonin (5-HT) receptor activation. Experiments were designed to determine whether some of the numerous effects of amphetamine on behavior can be ascribed to actions of the drug on 5-HT mechanisms. Catecholamine depletion with alpha-methyl-p-tyrosine did not prevent the amphetamine syndrome. However, 5-HT depletion with 5,7-dihydroxytryptamine or with p-chlorophenylalanine did prevent the syndrome. The degree of syndrome inhibition by p-chlorophenylalanine was correlated with the extent of 5-HT depletion. Normal responsiveness to amphetamine in p-chlorophenylalanine-treated rats was restored by 5-hydroxytryptophan, the precursor of 5-HT. Furthermore, methysergide, a 5-HT receptor blocker, prevented the amphetamine syndrome, whereas catecholamine blockers, phenoxybenzamine and pimozide, were ineffective. The results suggest that when amphetamine causes the signs of the syndrome it does so by activating 5-HT receptors in the brain, probably by displacement of endogenous 5-HT.
Authors:
R S Sloviter; E G Drust; J D Connor
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  206     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1978 Aug 
Date Detail:
Created Date:  1978-10-27     Completed Date:  1978-10-27     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  348-52     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
5,7-Dihydroxytryptamine / pharmacology
5-Hydroxytryptophan / pharmacology
Animals
Behavior, Animal / drug effects*
Brain Chemistry / drug effects
Dextroamphetamine / pharmacology*
Dopamine / analysis
Male
Norepinephrine / analysis
Rats
Receptors, Serotonin / drug effects
Serotonin / analysis,  physiology*
Time Factors
Chemical
Reg. No./Substance:
0/Receptors, Serotonin; 31363-74-3/5,7-Dihydroxytryptamine; 50-67-9/Serotonin; 51-41-2/Norepinephrine; 51-64-9/Dextroamphetamine; 56-69-9/5-Hydroxytryptophan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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