Evidence for serotonergic modulation of progesterone-induced hyperphagia, depression and algesia in female mice.
The acute administration of the neurosteroid precursor, progesterone (10 mg/kg, s.c.) produced significant hyperphagia in female mice as observed at 0.5-, 1-, 2- and 3-h time intervals. At this dose progesterone also produced significant increase in immobility period duration in Porsolt's forced swim test and nociceptive response in hot-plate and tail-flick tests. Treatment with direct (quipazine, 5 mg/kg, i.p.) and indirect (fluoxetine, 10 mg/kg, i.p.) acting serotonergic agents per se produced significant hypophagia, decrease in immobility period and induced analgesic effect in hot-plate and tail-flick test. Further, treatment with both fluoxetine (10 mg/kg, i.p.) and quipazine (5 mg/kg, i.p.) significantly reversed progesterone-induced hyperphagia, depression and algesia in the female mice. Pretreatment with seganserin, a 5-HT(2) receptor antagonist (2 mg/kg, i.p.) significantly reversed fluoxetine and quipazine-induced antidepressant and analgesic effects. Seganserin reversed quipazine-induced hypophagia but in a replicate study it failed to reverse fluoxetine-induced hypophagia. Further, seganserin, 2 mg/kg, i.p., significantly reversed the suppressive effect of fluoxetine and quipazine on progesterone-induced hyperphagia, depression and algesia in hot-plate test. Seganserin also reversed the suppressive effect of fluoxetine and quipazine on progesterone-induced algesia in hot-plate test. These data suggest that the modulation of progesterone-induced effects by these serotonergic agents possibly involve 5-HT(2) receptor mechanisms. Further, the study underscores the use of serotonergic agents for the treatment of eating and affective disorders caused by the regular changes or disturbances of ovarian steroid levels in females.
Kaur
Gurpreet
G
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.
Kulkarni
Shrinivas K
SK
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003863:Depression / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006963:Hyperphagia / Q000378:metabolism* / Q000503:physiopathology; D008597:Menstrual Cycle / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism*; D011814:Quipazine / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology
D000700:Analgesics; D018687:Antidepressive Agents, Second-Generation; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005473:Fluoxetine; C046301:seganserin; D012701:Serotonin; D011374:Progesterone; D011814:Quipazine