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Vinpocetine, a Phosphodiesterase Type 1 Inhibitor, Mitigates Locomotor Hyperactivity in Female Mice Exposed to Lead
Ulisses C Araujo1, Fernanda Nunes1, Bruno S Gonçalves1
1Departamento de Ciências Fisiológicas, Universidade do Estado do Rio de Janeiro, Av. Prof. Manoel de Abreu 444, 5 andar, Vila Isabel, Rio de Janeiro 20550-170, RJ, Brazil.
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.
Insights
Vinpocetine reversed lead-induced hyperactivity in female mice by targeting cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) pathways. This suggests these signaling pathways are key in lead-induced behavioral changes.
Area of Science:
- Neuroscience
- Developmental Toxicology
Background:
- Disruptions in cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling are linked to hyperactivity in rodent models.
- Early-life exposure to lead is a potential neurodevelopmental toxicant.
Purpose of the Study:
- To investigate if vinpocetine, a phosphodiesterase type 1 inhibitor, can mitigate lead-induced locomotor hyperactivity.
- To explore the role of cAMP and cGMP signaling in lead's effects on behavior.
Main Methods:
- Swiss mice were exposed to lead (90 ppm) from gestation through postnatal day 10.
- Locomotor activity was assessed at postnatal day 30 after administering vinpocetine or vehicle.
- Blood lead levels were measured at postnatal day 10.
Main Results:
- Lead-exposed females exhibited significantly increased locomotor activity compared to controls.
- Lead-exposed males did not show significant changes in locomotor activity.
- Vinpocetine treatment effectively reversed the hyperactivity observed in lead-exposed females.
Conclusions:
- Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling pathways are implicated in lead-induced hyperactivity.
- Vinpocetine demonstrates potential therapeutic effects against lead neurotoxicity in females.
