Rolipram improves facilitation of contextual fear extinction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease.

Cognitive impairment often occurs in Parkinson's disease (PD), but the mechanism of onset remains unknown. Recently, we reported that PD model mice produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) show facilitation of hippocampal memory extinction, which may be the cause of cognitive impairment in PD. When we examined the cAMP/CREB signaling in the hippocampus, decreased levels of cAMP and phosphorylated CREB were observed in the dentate gyrus (DG) of MPTP-treated mice. Administration of rolipram improved the memory deficits with concomitant recovery of cAMP and phosphorylated CREB levels, suggesting that reduced cAMP/CREB signaling in the DG leads to cognitive impairment in MPTP-treated mice.