Document Detail

Food restriction and streptozotocin differentially modify sensitivity to the hypothermic effects of direct- and indirect-acting serotonin receptor agonists in rats.
MedLine Citation:
PMID:  19379724     Owner:  NLM     Status:  MEDLINE    
Food restriction and experimentally-induced diabetes (streptozotocin) can modify serotonin (5-HT) neurotransmission and sensitivity to drugs acting on 5-HT systems. This study examined the effects of food restriction and streptozotocin on the hypothermic effects of the 5-HT(1A) receptor agonist (+)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT), the 5-HT(2) receptor agonist (+/-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (DOM), the 5-HT releaser fenfluramine, and the selective 5-HT reuptake inhibitor (SSRI) fluoxetine. All four drugs significantly decreased body temperature in free feeding rats. Limiting rats to 10 g/day of food for 7 days decreased body weight and sensitivity to 8-OH-DPAT induced hypothermia, without affecting sensitivity to DOM, fenfluramine, or fluoxetine induced hypothermia. Subsequently, 7 days of free feeding restored body weight and sensitivity to 8-OH-DPAT. Sensitivity to all drugs was significantly decreased 7 days after 50 mg/kg streptozotocin; subsequently, 10 days of insulin replacement restored sensitivity to all drugs. These results extend to body temperature the observation that food restriction and experimentally-induced diabetes differentially modify sensitivity to drugs acting on 5-HT systems and they further suggest that the clinical response to therapeutic drugs acting on 5-HT systems might be impacted by nutritional and insulin status.
Jun-Xu Li; Wouter Koek; Charles P France
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-04-18
Journal Detail:
Title:  European journal of pharmacology     Volume:  613     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-01     Completed Date:  2009-08-28     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  60-3     Citation Subset:  IM    
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MeSH Terms
2,5-Dimethoxy-4-Methylamphetamine / toxicity
8-Hydroxy-2-(di-n-propylamino)tetralin / toxicity
Body Temperature / drug effects
Body Weight / drug effects
Fenfluramine / toxicity
Hypothermia / chemically induced*,  physiopathology
Rats, Sprague-Dawley
Serotonin Receptor Agonists / toxicity*
Serotonin Uptake Inhibitors / toxicity
Streptozocin / administration & dosage,  pharmacology*
Grant Support
Reg. No./Substance:
0/Serotonin Receptor Agonists; 0/Serotonin Uptake Inhibitors; 15588-95-1/2,5-Dimethoxy-4-Methylamphetamine; 2DS058H2CF/Fenfluramine; 5W494URQ81/Streptozocin; 78950-78-4/8-Hydroxy-2-(di-n-propylamino)tetralin

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