Spontaneous alternation and stereotypical behaviour in deer mice: response to escitalopram and levetiracetam.

Abstract

Obsessive-compulsive disorder is varyingly associated with cognitive impairment, that is, deficits in spatial working memory, although it seems unlikely that this is generalised across all domains of functioning. Further, it is unclear whether symptoms will respond to potentially novel, non-serotonergic drugs that have shown promise as so-called cognitive enhancers. Here, we studied low (Norm-N; n = 31) and compulsive-like high (Comp-H; n = 34) stereotypical deer mice (Peromyscus maniculatus bairdii) to establish (1) whether there is a relationship between stereotypical intensity and working memory ability as measured by spontaneous T-maze arm alternation and (2) if and how stereotypy and its association with changes in working memory, would respond to the known anti-compulsive agent, escitalopram, and the proposed cognitive enhancer, levetiracetam. After assessing the stereotypical and alternation behaviour of all animals at baseline, they were divided into three socially housed drug exposure groups, that is, water control (n = 11 per phenotype), escitalopram 50 mg/kg/d (n = 11 per phenotype) and levetiracetam 75 mg/kg/d (Norm-N: n = 9; Comp-H: n = 12). Drugs were administered for 28 days before stereotypy and alternation assessment were repeated. The present data indicate a weak negative relationship between stereotypical intensity and spontaneous alternation. While levetiracetam increased the time spent engaging in normal rodent activity by Comp-H, but not Norm-N animals, neither of the interventions affected the expression of Comp-H behaviour or the alternation behaviour of deer mice. In conclusion, this work points to some degree of cognitive involvement in Comp-H expression, which should be explored to further our understanding of compulsive-like stereotypy.