Arsenic toxicity is a major health issue worldwide, known to cause neurotoxicity with complex etiology. PDE1 inhibitors and PDE4 inhibitors are known to enhance the brain condition manifesting similar neurological and behavioral phenotypes. The neurotoxicity was induced by administering sodium arsenite containing water. The pharmacological consequences of administering rolipram and vinpocetine in sodium arsenite induced behavioral phenotypes (spatial, short and long term memory, motor coordination) was assessed. The effect on brain and body weight was observed. Additionally, the effect of rolipram and vinpocetine on CREB and P-CREB expression was also analyzed by immunohistochemistry. The improvement in the behavioral phenotype was found and also a significant increase in the expression of CREB and P-CREB was observed. This improvement in the learning, memory power, reflexes and motor coordination, may be due to the enhanced CREB and P-CREB neurons expressions by rolipram and vinpocetine. Thus, PDE4 and PDE1 inhibition by rolipram and vinpocetine may be a possible target to study the arsenic induced neurotoxicity and behavioral deficit .