Chronic exposure to Ro20-1724 protects dopaminergic neurons in vitro against the neurotoxic action of N-methyl-d-aspartate and 1-methyl-4-phenylpyridinium

Using organotypic cultures of rat ventral mesencephalon, the effects of chronic (12–15 day) exposure to the type IV cAMP phosphodiesterase inhibitor, Ro20-1724, were examined. At concentrations of 10⁻⁸–10⁻⁵ M, Ro20-1724 alone had no effect upon the number of tyrosine hydroxylase-positive neurons or upon neurite outgrowth. However, the drug offered significant protection, with maximum effect at 10⁻⁶ M, against subsequent acute (48 h) exposure to the neurotoxic agents 1-methyl-4-phenylpyridinium (MPP⁺) and N-methyl-d-aspartate (NMDA).