Behavioral mechanisms for the anorectic action of the serotonin (5-HT) uptake inhibitor sertraline in rats: comparison with directly acting 5-HT agonists.
The 5-HT uptake inhibitor, sertraline (5-40 mumol/kg, IP) reduced the volume of milk consumed by food-deprived rats during a 30-min test (ID50 = 12 mumol/kg). Observations using a time-sampling method revealed that sertraline shortened meal duration (ID50 = 14 mumol/kg) by decreasing feeding and increasing resting without altering nonfeeding activity or the overall sequence of behavior that characterizes normal satiety. In separate experiments, analysis of videotapes demonstrated that sertraline (10 mumol/kg) decreased not only the time that rats fed but also their actual rate of intake. In comparison, doses of the direct 5-HT agonists, mCPP (1-[3-chlorophenyl]piperazine), RU 24969 (5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole), and DOI (1-[2,5-dimethoxy-4-iodophenyl]-2-amino-propane) that produced similar anorectic effects altered either feeding time or rate but not both. DOI also disrupted the continuity of feeding and the 5-HT agonist, 8-OH-DPAT (8-hydroxy-di-N-propylamino tetralin) produced marked stereotypy at anorectic doses. Together, these results imply that stimulating a number of different serotonergic mechanisms can reduce food intake in rats. Sertraline appears to accelerate the onset of normal satiety, presumably by enhancing physiological actions of endogenous 5-HT.
Simansky
K J
KJ
Department of Pharmacology, Medical College of Pennsylvania, Eastern Pennsylvania Psychiatric Institute, Philadelphia 19129.
Vaidya
A H
AH
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012527:Satiation / Q000187:drug effects; D020280:Sertraline; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000662:Amphetamines; D007211:Indoles; D010879:Piperazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D015057:1-Naphthylamine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D020280:Sertraline; C015068:1-(3-chlorophenyl)piperazine