Our lab recently validated the deer mouse (Peromyscus maniculatus bairdii) as model of OCD (Korff et al., 2007). Deer mice are useful models in that they engage in spontaneous stereotypic behaviour. This study compared cAMP levels, PDE4 activity, and PDE4 isoform expression of pharmacologically naïve deer mice to that of a non-stereotypic strain; C57Bl. Uniquely, deer mice display different degrees stereotypy, e.g. low versus high rates (Powell et al., 1999). Moreover, for the purpose of this study a distinction was made between low stereotypic (LSB), high stereotypic (HSB) and non-stereotypic deer mice. The degree of stereotypy in Peromyscus was linked to the amount of cAMP under basal conditions in the prefrontal cortex and striatum, and correlated with PDE4 activity and expression in matching brain regions. HSB mice (8.51 pmol/mg prot) presented with the highest prefrontal cortex and striatal cAMP levels compared to LSB (7.05), non-stereotypic (6.84), and C57Bl mice (6.73). PDE4 activity was significantly higher in deer mice (3.81 pmol/min/mg prot) compared to C57Bl mice (1.86 pmol/min/mg prot). Immunobloting of PDE4 revealed that deer mice express significantly more prefrontal cortex PDE 4B4 and 4D4 and significantly less PDE 4A5, 4B1, and 4D1 isoforms compared to C57Bl. Striatal expression of PDE 4A5, 4B4, and 4D1 was significantly lower, and that of PDE 4D4 was significantly higher in deer mice compared to C57Bl. In summary, neurochemical and molecular characterization of deer mice versus C57Bl mice indicate that raised stereotypic behaviour is characteristic of the deer mouse, and that raised stereotypic behaviour in these animals are associated with differential expression of select isoforms of the PDE4 family, which drive cellular release of striatal and prefrontal cAMP.