Food restriction and streptozotocin differentially modify sensitivity to the hypothermic effects of direct- and indirect-acting serotonin receptor agonists in rats.
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.
Li
Jun-Xu
JX
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Koek
Wouter
W
France
Charles P
CP
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000633:toxicity; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000633:toxicity; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D005277:Fenfluramine / Q000633:toxicity; D007035:Hypothermia / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000633:toxicity*; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity; D013311:Streptozocin / Q000008:administration & dosage / Q000494:pharmacology*
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D005277:Fenfluramine; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013311:Streptozocin