LHRH antagonist attenuates the effect of fluoxetine on marble-burying behavior in mice.
Leuprolide--a luteinizing hormone-releasing hormone (LHRH) agonist, dose dependently (100, 200 and 300 microg/kg, s.c.) inhibited marble-burying behavior in mice, which was comparable to that of fluoxetine (10 and 15 mg/kg, i.p.)--a drug used in the treatment of obsessive-compulsive disorder. Co-administration of sub-effective dose of leuprolide (50 microg/kg) and fluoxetine (5 mg/kg) significantly inhibited marble-burying-behavior. Pre-treatment with parachlorophenylalanine [300 mg/kg, i.p. (x3 days)]--a serotonin depleting agent, reversed the effect of fluoxetine, whereas partially attenuated the effect of leuprolide. Further, LHRH antagonist pre-treatment (2.5 microg/mouse, s.c.) completely blocked the effect of leuprolide and reduced the effect of fluoxetine. Motor activity remained unaffected after all treatments. In conclusion, the findings suggest that fluoxetine also implicates LHRH in its anti-compulsive effect.
Uday
Gaikwad
G
Department of Pharmaceutical Sciences, Rashtrasant Tukdoji Maharaj Nagpur University, Nagpur - 440 033, Maharashtra, India.
Pravinkumar
Bhutada
B
Manish
Wanjari
W
Sudhir
Umathe
U
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D010134:Fenclonine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology* / Q000627:therapeutic use; D007987:Gonadotropin-Releasing Hormone / Q000187:drug effects* / Q000378:metabolism; D016729:Leuprolide / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D009842:Oligopeptides / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology* / Q000627:therapeutic use; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D010134:Fenclonine; D005473:Fluoxetine; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide; D009842:Oligopeptides; D011619:Psychotropic Drugs; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C521598:pyroglutamyl-phenylalanyl-tryptophyl-seryl-tyrosyl-alanyl-leucyl-arginyl-prolyl-glycinamide