Effects of conantokins on L-3,4-dihydroxyphenylalanine-induced behavior and immediate early gene expression

Conantokins, peptides from Conus snails, are N-methyl-D-aspartate (NMDA) re ceptor antagonists. NMDA receptor antagonists potentiate L-3,4-dihydroxyphe nylalanine (L-DOPA)-induced rotation in 6-hydroxydopamine-treated rodents, an index of anti-parkinsonian potential. This study examined the effects of conantokin-G, conantokin-T(G), CGS 19755, and ifenprodil on L-DOPA-induced contralateral rotation and immediate early gene (IEG) expression in 6-hydr oxydopamine-treated rats. Rats received unilateral infusions of 6-hydroxydo pamine into the medial forebrain bundle. Three weeks later, rats were treat ed with an NMDA receptor antagonist, followed by an injection of L-DOPA. Co ntralateral rotations were recorded for 2 h. In addition, the expression of zif268 and c-fos were examined. Conantokin-G, conantokin-T(G), and CGS 197 55 potentiated L-DOPA-induced rotation. Conantokin-G and ifenprodil had no effect on L-DOPA-induced IEG expression, whereas conantokin-T(G) and CGS 19 755 attenuated expression. These data suggest that conantokins may be usefu l in treating Parkinson's disease. Furthermore, different NMDA receptor ant agonists have distinct effects on striatal gene expression. (C) 2000 Elsevi er Science B.V. All rights reserved.