Vinpocetine, a Phosphodiesterase Type 1 Inhibitor, Mitigates Locomotor Hyperactivity in Female Mice Exposed to Lead During Development.

Abstract

Background/Objectives Studies in rodents indicate that disruptions in both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling pathways are involved in the development of hyperactive behavior. We examined whether vinpocetine, a phosphodiesterase type 1 inhibitor that enhances brain cAMP and cGMP levels, could mitigate locomotor hyperactivity in mice exposed to lead during early development. Methods Swiss mice were exposed to 90 ppm of lead in their drinking water throughout gestation and the first ten postnatal days. At postnatal day 10 (PN10), blood lead levels (BLLs) were about 30 µg/dL. At PN30, animals either received vinpocetine (20 mg/kg, i.p.) or a vehicle 4 h before the evaluation of locomotor activity in the open field. Results Lead-exposed males did not display differences in locomotor activity compared to controls, while lead-exposed females showed a significant increase in locomotion. Vinpocetine treatment significantly reversed the lead-induced hyperactivity in females. Conclusions These findings suggest that the cAMP and cGMP signaling pathways play a role in the hyperactivity induced by lead exposure.