Food restriction and streptozotocin differentially modify sensitivity to the hypothermic effects of direct- and indirect-acting serotonin receptor agonists in rats.

Abstract

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.

• Authors: Jun-Xu Li, Wouter Koek, Charles P France
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 613 Issue 1-3 Pg. 60-3 (Jun 24 2009) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 19379724 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Serotonin Receptor Agonists
• Serotonin Uptake Inhibitors
• DOM 2,5-Dimethoxy-4-Methylamphetamine
• Fenfluramine
• Streptozocin
• 8-Hydroxy-2-(di-n-propylamino)tetralin

Topics

• DOM 2,5-Dimethoxy-4-Methylamphetamine (toxicity)
• 8-Hydroxy-2-(di-n-propylamino)tetralin (toxicity)
• Animals
• Body Temperature (drug effects)
• Body Weight (drug effects)
• Diet
• Fenfluramine (toxicity)
• Hypothermia (chemically induced, physiopathology)
• Male
• Rats
• Rats, Sprague-Dawley
• Serotonin Receptor Agonists (toxicity)
• Selective Serotonin Reuptake Inhibitors (toxicity)
• Streptozocin (administration & dosage, pharmacology)