title: Increased marble-burying behavior in ethanol-withdrawal state: modulation by gonadotropin-releasing hormone agonist.
abstract: A characteristic behavior in alcohol abstinence state indicates the possibility of obsessive-compulsive behavior in alcoholics. Ethanol is known to reduce hypothalamic synthesis, release, and mRNA expression of gonadotropin-releasing hormone (GnRH) that modulates serotonergic, dopaminergic, and glutamatergic systems, which experience adaptive changes on chronic exposure to ethanol. Such changes are also evident in obsessive-compulsive disorder. Therefore, it was proposed to investigate the effect of ethanol-withdrawal on marble-burying behavior in mice, particularly because it simulates some aspects of obsessive-compulsive behavior; further, the influence of GnRH agonist was studied on the same. Ethanol-withdrawal state was induced after its chronic administration, and marble-burying behavior was observed at 0, 6, 24, 48, and 96 h interval. Further, the influence of leuprolide--a GnRH agonist (50-600 microg/kg, s.c.) or fluoxetine (5-30 mg/kg, i.p.) was investigated on ethanol-withdrawal-induced changes in marble-burying behavior. The results indicated that ethanol-withdrawal led to a gradual increase in marble-burying behavior upto 48 h with peak at 24 h interval. Administration of leuprolide (100-600 microg/kg, s.c.), 30 min prior to 24 h interval, dose dependently reduced ethanol-withdrawal-induced increase in marble-burying behavior, and this effect was comparable to that of fluoxetine (15 and 30 mg/kg, i.p.). Further, twice daily administration of leuprolide (50 microg/kg, s.c), concomitant with ethanol, prevented the gradual increase in marble-burying behavior after ethanol-withdrawal and this effect was comparable to fluoxetine (5 mg/kg, i.p.). In conclusion, ethanol-withdrawal on chronic administration increases marble-burying behavior in mice; its development and expression is attenuated by leuprolide.
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440033, Maharashtra, India. umathesn@hotmail.com <umathesn@hotmail.com>
authors.forename: Sudhir
authors.initials: S
authors.lastname: Umathe
authors.forename: Pravinkumar
authors.initials: P
authors.lastname: Bhutada
authors.forename: Pankaj
authors.initials: P
authors.lastname: Dixit
authors.forename: Varsha
authors.initials: V
authors.lastname: Shende
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D000431:Ethanol / Q000009:adverse effects*; D005473:Fluoxetine / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D016729:Leuprolide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D005473:Fluoxetine; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide; D017367:Selective Serotonin Reuptake Inhibitors