Document Detail


Alterations in alcohol consumption, withdrawal seizures, and monoamine transmission in rats treated with phentermine and 5-hydroxy-L-tryptophan.
MedLine Citation:
PMID:  16416445     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have previously shown that coadministration of the dopamine (DA) agonist phentermine plus the serotonergic agonist fenfluramine suppresses alcohol intake and withdrawal seizures in rats. In the present study, phentermine and the serotonin (5-HT) precursor, 5-hydroxy-L-tryptophan (5-HTP), were administered alone, or in combination, to rats fed on a 6% alcohol-containing diet or an isocaloric control diet. Following a 9-h withdrawal period from the alcohol-containing diet, phentermine enhanced the effects of 5-HTP on both reduction of alcohol withdrawal seizures as well as changes in striatal serotonin. Food intake was monitored for 24 h after drug treatment, and neurochemical measures were examined at various time points. Phentermine alone reduced food intake in all diet conditions, but this anorectic effect was followed by hyperphagia in control rats. Phentermine plus 5-HTP reduced the consumption of the alcohol-containing diet, while its effects on consumption of control diets were mixed. In vivo microdialysis in rat nucleus accumbens revealed that phentermine increased extracellular DA, whereas 5-HTP caused marked elevations in extracellular 5-HT. Coadministration of phentermine and 5-HTP evoked simultaneous elevations in extracellular DA and 5-HT that mirrored the effects of each drug alone. Collectively, these findings show that coadministered phentermine plus 5-HTP is effective in reducing alcohol intake and suppressing alcohol withdrawal seizures. These therapeutic actions may be related to elevations in synaptic DA and 5-HT in critical brain regions.
Authors:
A K Halladay; G C Wagner; A Sekowski; R B Rothman; M H Baumann; H Fisher
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Synapse (New York, N.Y.)     Volume:  59     ISSN:  0887-4476     ISO Abbreviation:  Synapse     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-01-24     Completed Date:  2006-05-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8806914     Medline TA:  Synapse     Country:  United States    
Other Details:
Languages:  eng     Pagination:  277-89     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Rutgers University, New Brunswick, New Jersey 08901, USA.
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MeSH Terms
Descriptor/Qualifier:
5-Hydroxytryptophan / therapeutic use*
Alcohol Drinking / drug therapy*
Alcohol Withdrawal Seizures / drug therapy*
Analysis of Variance
Animals
Behavior, Animal / drug effects
Biogenic Monoamines / metabolism*
Brain Chemistry / drug effects
Central Nervous System Depressants / adverse effects
Central Nervous System Stimulants / therapeutic use*
Dose-Response Relationship, Drug
Drug Interactions
Ethanol / adverse effects
Male
Phentermine / therapeutic use*
Rats
Rats, Long-Evans
Time Factors
Grant Support
ID/Acronym/Agency:
ES05022/ES/NIEHS NIH HHS; ES11259/EPA82939101/ES/NIEHS NIH HHS; ES11729/ES/NIEHS NIH HHS; NS43981/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Biogenic Monoamines; 0/Central Nervous System Depressants; 0/Central Nervous System Stimulants; 122-09-8/Phentermine; 56-69-9/5-Hydroxytryptophan; 64-17-5/Ethanol

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


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