No effect of riluzole and memantine on learning deficit following quinpirole sensitization - An animal model of obsessive-compulsive disorder
Abstract
Rationale: Chronic quinpirole (QNP) sensitization is an established animal model relevant to obsessive-compulsive disorder (OCD) that has been previously shown to induce several OCD-like behavioral patterns, such as compulsive-like checking and increased locomotion. Objectives: In current study we explored the effect of antiglutamatergic drugs, memantine and riluzole, on cognitive and behavioral performance of QNP sensitized rats.
Methods: During habituation phase, the rats (N = 56) were injected with QNP (0.25 mg/kg) or saline solution (every other day up to 10 injections) and placed into rotating arena without foot shocks for 50-min exploration. Active place avoidance task in rotating arena with unmarked to-be-avoided shock sector was used during acquisition phase.
Rats were injected with memantine (1 mg/kg or 5 mg/kg), riluzole (1 mg/kg or 5 mg/kg) or saline solution 30 min before the trial and with QNP (0.25 mg/kg) or saline right before they were placed inside the rotating arena with 60 degrees unmarked shock sector. Locomotion and number of entrances into the shock sector were recorded.
Results: QNP sensitization led to a robust deficit in place learning. However, neither memantine nor riluzole did reverse or alleviate the deficit induced by QNP.
Contrarily, memantine significantly aggravated QNP induced deficit. Conclusions: The exacerbation of cognitive deficit following antiglutamatergic agents could be mediated by decreased glutamate concentration in nucleus accumbens and decreased hippocampal activation in the QNP sensitization model.