title: Effects of mood stabilizers on marble-burying behavior in mice: involvement of GABAergic system.
abstract: BACKGROUND
  Obsessive-compulsive disorder (OCD) is characterized by recurrent unwanted thoughts (obsessions), usually accompanied by repetitive behaviors (compulsions) intended to alleviate anxiety. Marble-burying behavior is a pharmacological model for study of OCD.
  
  
  OBJECTIVE
  In the present study, we examined the effects of mood stabilizers on marble-burying behavior in mice, as well as the role of GABA receptors in this behavior.
  
  
  METHODS
  The effects of treatment with valproate, carbamazepine, lithium carbonate, lamotrigine, muscimol and baclofen on marble-burying behavior in mice were evaluated.
  
  
  RESULTS
  Valproate (10, 30 and 100 mg/kg, i.p.) and carbamazepine (30 and 100 mg/kg, p.o.) significantly reduced marble-burying behavior without affecting total locomotor activity in ICR mice. Lamotrigine (30 mg/kg, i.p.) also significantly reduced marble-burying behavior in ddY mice. On the other hand, lithium carbonate (10, 30 and 100 mg/kg, i.p.) reduced total locomotor activity without affecting marble-burying behavior in ddY mice. The selective GABA(A) receptor agonist muscimol (1 mg/kg) significantly reduced marble-burying behavior without affecting total locomotor activity, whereas the selective GABA(B) receptor agonist baclofen (3 mg/kg) reduced total locomotor activity without affecting marble-burying behavior. Moreover, the selective GABA(A) receptor antagonist bicuculline (3 mg/kg) significantly counteracted the decrease in marble-burying induced by the administration of muscimol (1 mg/kg) and valproate (100 mg/kg).
  
  
  CONCLUSIONS
  These results suggest that GABAergic mechanism is involved in marble-burying behavior, and that valproate, carbamazepine and lamotrigine reduce marble-burying behavior. Moreover, valproate reduces marble-burying behavior via a GABA(A) receptor-dependent mechanism.
authors.affiliation: Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan. n-egashi@pharm.med.kyushu-u.ac.jp
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.forename: Moe
authors.initials: M
authors.lastname: Abe
authors.forename: Atsunori
authors.initials: A
authors.lastname: Shirakawa
authors.forename: Tomiko
authors.initials: T
authors.lastname: Niki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Ryozo
authors.initials: R
authors.lastname: Oishi
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology; D002220:Carbamazepine / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000077213:Lamotrigine; D016651:Lithium Carbonate / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D011963:Receptors, GABA-A / Q000187:drug effects; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D011963:Receptors, GABA-A; D014227:Triazines; D009118:Muscimol; D016651:Lithium Carbonate; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D001418:Baclofen; D000077213:Lamotrigine; D001640:Bicuculline