The combination of sub effective doses of agmatine and ketamine reduces obsessive compulsive like behavior of mice in marble burying test


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KELEŞ R. M. , HAZAR A. N. , CEREN Ş., ÜNAL G., ARICIOĞLU F.

30th The International College of Neuropsychopharmacology (CINP) Congress, Seul, Güney Kore, 3 - 05 Temmuz 2016, sa.1

  • Basıldığı Şehir: Seul
  • Basıldığı Ülke: Güney Kore

Özet

Objective: Obsessive compulsive disorder (OCD) is a debilitating psychiatric disorder still having lack of effective treatment of which the pathophysiology has been linked to glutamatergic dysfunction. Ketamine, having rapid antidepressant effect, was shown to reduce OCD symptoms supporting the glutamatergic perspective (1,2). Agmatine, an imidazoline and alpha adrenergic binding agent is an N-methyl-D-aspartate (NMDA) receptor antagonist and nitric oxide sythase inhibitor. It has recently been shown to reduce compulsive-like behaviors of mice in the marble burying (MB) test at a dose of 20mg/kg but not 10mg/kg (3). Herein, we examined possible potantialization of ketamine and agmatine in anticompulsive-like effect in marble burying test. Methods: Balb/c mice in both sexes (25–40g) were divided into Control (saline), Ketamine (3mg/kg), Agmatine (10mg/kg), Ketamine+Agmatine (3mg/kg+10mg/kg) groups (n=10–20 in each). MB test was applied 30min after i.p. drug administrations. In the marble burying test, 20 glass marbles, each about 4cm apart, are arrayed on the surface of 5cm thick sawdust bedding. The number of marbles buried (to 2/3 their depth) in a 30min session were counted. Open field test was also conducted for locomotor activity. One-way analysis of variance (ANOVA) was used for statistical analysis followed by Tukey’s test. Results: The number of marbles buried was not significantly different in agmatine (p>0.05) or ketamine (p>0.05) alone groups compared to control. When combined together in the same dosage regimen, the number of marbles buried was statistically less than control group (p<0.05). Conclusions: When administered alone at sub-effective doses, neither ketamine nor agmatine reduced compulsive-like behaviors. However, the combination of them resulted in potantialization in anticompulsive-like effects. It could be of interest to identify shared or distinct mechanisms of these molecules possibly responsible for the proposed behavioral manifestation seen in this compulsive model.