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