Temperature, food intake, and locomotor activity effects of a 5-HT3 receptor agonist and two 5-HT3 receptor antagonists in rats.
This study investigated three physiologic functions known to be modulated by serotonin-temperature, food intake and locomotor activity - using the 5-HT3 receptor agonist, m-chlorophenylbiguanide (m-CPBG), and two 5-HT3 antagonists, MDL-72222 and ondansetron. m-CPBG produced dose-dependent elevations in rectal temperature. MDL-72222, which had no effects on temperature when given alone, significantly attenuated m-CPBG-induced hyperthermia. Food intake in food-deprived rats was reduced during the first hour by the highest dose of m-CPBG. Food intake was also dose-dependently reduced by MDL-72222; m-CPBG plus MDL-72222 led to greater reductions in food intake. Food intake in freely fed rats was unaffected by m-CPBG or MDL-72222. Locomotor activity was unaffected by m-CPBG, but was dose-dependently reduced by MDL-72222, an effect which may have contributed to its hypophagic effects. Ondansetron, used in ten-fold lower doses than MDL-72222, was inactive in all of these paradigms. These data: (1) provide some evidence for 5-HT3 receptor-mediated changes in temperature; (2) are in agreement with two prior studies which reported locomotor activity reductions following 5-HT3 antagonists; but (3) do not support an important role for 5-HT3 receptors in the regulation of food intake in rats.
Mazzola-Pomietto
P
P
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Aulakh
C S
CS
Murphy
D L
DL
D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology
D001645:Biguanides; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014326:Tropanes; D017294:Ondansetron; C065734:1-(3-chlorophenyl)biguanide; C042253:bemesetron