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) receptor antagonists. NMDA receptor antagonists potentiate L-3,4-dihydroxyphenylalanine (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-hydroxydopamine-treated rats. Rats received unilateral infusions of 6-hydroxydopamine into the medial forebrain bundle. Three weeks later, rats were treated with an NMDA receptor antagonist, followed by an injection of L-DOPA. Contralateral rotations were recorded for 2 h. In addition, the expression of zif268 and c-fos were examined. Conantokin-G, conantokin-T(G), and CGS 19755 potentiated L-DOPA-induced rotation. Conantokin-G and ifenprodil had no effect on L-DOPA-induced IEG expression, whereas conantokin-T(G) and CGS 19755 attenuated expression. These data suggest that conantokins may be useful in treating Parkinson's disease. Furthermore, different NMDA receptor antagonists have distinct effects on striatal gene expression.
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Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East, Room 201, Salt Lake City, UT 84112-5820, USA.
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McCabe
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Keefe
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D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D020916:Conotoxins / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D051766:Early Growth Response Protein 1; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D017781:Genes, Immediate-Early / Q000187:drug effects* / Q000502:physiology; D016762:Genes, fos / Q000187:drug effects* / Q000502:physiology; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010875:Pipecolic Acids / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism
D000978:Antiparkinson Agents; D020916:Conotoxins; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D018691:Excitatory Amino Acid Antagonists; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008978:Mollusk Venoms; D010455:Peptides; D010875:Pipecolic Acids; D010880:Piperidines; D014157:Transcription Factors; C063571:conantokin-T; D007980:Levodopa; C053672:selfotel; C055407:conotoxin GV; C010739:ifenprodil