Glutamatergic regulation of striatal peptide gene expression in rats.
The mRNA levels encoding enkephalin and substance P were measured in the rat striatum following cortical ablation, blockade of N-methyl-D-aspartate (NMDA) receptors or inhibition of glutamate release by lamotrigine. Unilateral ablation of the cerebral cortex resulted in a decrease of substance P mRNA levels particularly in the rostral dorsolateral and dorsomedial striatum ipsilateral to the lesion. There was a similar trend for a reduction in levels of enkephalin mRNA. Continuous, intrastriatal infusion of the competitive NMDA receptor antagonist, 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, (CPP, 0.12 and 1.2microg/day) decreased both enkephalin mRNA and substance P mRNA in dose-dependent manner evenly throughout the striatum adjacent to the infusion site. Following subchronic administration of the presumed glutamate release inhibitor, lamotrigine (5 and 20mg/kg IP) there was no significant alterations in either enkephalin mRNA or substance P mRNA levels in the striatum. Both enkephalin mRNA and substance P mRNA expression in the rat striatum appear tonically stimulated through postsynaptic NMDA receptor mediated mechanisms. This contrasts with differential dopaminergic modulation of peptides in striatal output neurons.
Jolkkonen
J
J
Neurodegenerative Diseases Research Centre, Biomedical Sciences Division, King's College, London.
Jenner
P
P
Marsden
C D
CD
D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism*; D017403:In Situ Hybridization; D000077213:Lamotrigine; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*; D014227:Triazines / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004745:Enkephalins; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D014227:Triazines; D013373:Substance P; D000077213:Lamotrigine