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 μg/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 μg/kg) and fluoxetine (5 mg/kg) significantly inhibited marble-burying-behavior. Pre-treatment with parachlorophenylalanine [300 mg/kg, i.p. (× 3 days)] — a serotonin depleting agent, reversed the effect of fluoxetine, whereas partially attenuated the effect of leuprolide. Further, LHRH antagonist pre-treatment (2.5 μg/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.