Effect of chronic treatment with TFMPP, a 5-HT1 receptor agonist, on food intake, weight gain, plasma insulin and neuropeptide mRNA expression in obese Zucker rats.
1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP), a 5-HT1 receptor agonist, decreases food intake in rats when given acutely. The present investigation was performed to study the chronic effects of TFMPP on food intake and weight gain in genetically obese Zucker rats. Neurochemical and endocrine data on possible mechanisms involved in the action of TFMPP were collected at the end of the study. TFMPP (4 mg/kg per day s.c.) significantly reduced food intake on the 1st and 7th days, but no longer on the 14th and 28th days. Reduced food intake was associated with decreased body weight gains during the first two weeks of treatment, but no effect was found thereafter. Plasma insulin concentration was significantly lowered by TFMPP treatment without impairment of glucose homeostasis. In situ hybridization analysis did not reveal changes in the expression of preprocorticotropin-releasing factor mRNA in the paraventricular nucleus or preproneuropeptide Y mRNA in the arcuate nucleus. Chronic TFMPP administration significantly reduced the density of 5-HT2 receptors, as measured by quantitative receptor autoradiography, in the claustrum and cerebral cortex, but not 5-HT1C receptor density in the choroid plexus. It is concluded that the anorectic and weight gain-lowering effects of TFMPP decrease during long-term treatment in obese Zucker rats.
Rouru
J
J
Department of Pharmacology, University of Turku, Finland.
Pesonen
U
U
Isaksson
K
K
Huupponen
R
R
Koulu
M
M
D000818:Animals; D001345:Autoradiography; D001786:Blood Glucose / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D007328:Insulin / Q000097:blood*; D008297:Male; D009479:Neuropeptides / Q000096:biosynthesis*; D009765:Obesity / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011924:Rats, Zucker; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects*
D001786:Blood Glucose; D007328:Insulin; D009479:Neuropeptides; D010879:Piperazines; D012333:RNA, Messenger; D017366:Serotonin Receptor Agonists; C018406:1-(3-trifluoromethylphenyl)piperazine; D003346:Corticotropin-Releasing Hormone