Antipsychotics regulate cyclic AMP-dependent protein kinase and phosphorylated cyclic AMP response element-binding protein in striatal and cortical brain regions in mice.

Adenosine 3',5'-monophosphate (cAMP) and cAMP-dependent protein kinase (PKA) signaling have been implicated in antipsychotic drug action. This study examines the effects of acute antipsychotic treatment using typical (haloperidol) and atypical (olanzapine) agents on cAMP signaling in dorsal striatum, nucleus accumbens and medial prefrontal cortex in mice. PKA catalytic subunit (PKA-c) and phosphorylated cAMP response element-binding protein (pCREB) levels were measured to evaluate antipsychotic drug effects. Nuclear PKA-c levels increased in the dorsal striatum after haloperidol and olanzapine treatment. In medial prefrontal cortex, olanzapine produced dose-dependent decreases in PKA-c and pCREB levels. The differential effects of typical versus atypical antipsychotic agents on PKA and pCREB in striatal and cortical regions illustrate the diverging actions of these agents on cAMP pathways.