Associations between nesting, stereotypy, and working memory in deer mice: response to levetiracetam

BACKGROUND: Some deer mice (Peromyscus maniculatus bairdii) exhibit various phenotypes of persistent behaviors. It remains unknown if and how said phenotypes associate with early-life and adult cognitive perturbations, and whether potentially cognitive enhancing drugs might modify such associations. Here, we explored the longitudinal relationship between early-life behavioral flexibility and the expression of persistent behavior in adulthood. We also investigated how said phenotypes might associate with working memory in adulthood, and how this association might respond to chronic exposure to the putative cognitive enhancer, levetiracetam (LEV). METHODS: 76 juvenile deer mice were assessed for habit-proneness in the Barnes maze (BM) and divided into two exposure groups (n = 37–39 per group), i.e., control and LEV (75 mg/kg/day). After 56 days of uninterrupted exposure, mice were screened for nesting and stereotypical behavior, and then assessed for working memory in the T-maze. RESULTS: Juvenile deer mice overwhelmingly utilize habit-like response strategies, regardless of LNB and HS behavior in adulthood. Further, LNB and HS are unrelated in terms of their expression, while LEV reduces the expression of LNB, but bolsters CR (but not VA). Last, an increased level of control over high stereotypical expression may facilitate improved working memory performance. CONCLUSION: LNB, VA and CR, are divergent in terms of their neurocognitive underpinnings. Chronic LEV administration throughout the entire rearing period may be of benefit to some phenotypes, e.g., LNB, but not others (CR). We also show that an increased level of control over the expression of stereotypy may facilitate improved working memory performance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43440-023-00484-2.