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

Abstract

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).