Ac. Adams et al., Effects of conantokins on L-3,4-dihydroxyphenylalanine-induced behavior and immediate early gene expression, EUR J PHARM, 404(3), 2000, pp. 303-313
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.