ly-306740 and Seizures

The effect of intrastriatal administration of LY306740, a specific NK-1 receptor antagonist, on the behavior and changes in gene expression elicited by the psychomotor stimulant, amphetamine, was studied. Acute administration of amphetamine (2.5 mg/kg, i.p.) caused an increase in behavioral activity and preproenkephalin, preprodynorphin and substance P mRNA expression in the striatum. When amphetamine-treated rats were pretreated with LY306740 (35 and 20 nmoles per side, intrastriatally), there was a significant decrease in amphetamine-induced behavioral activity. Quantitative in situ hybridization histochemistry revealed that both concentrations of LY306740 significantly decreased amphetamine-induced mRNA expression of all three neuropeptides. These data indicate that striatal NK-1 receptors modulate amphetamine-induced behavior and mRNA expression of neuropeptides in the rat striatum.

Topics: Acetamides; Amphetamine; Animals; Area Under Curve; Behavior, Animal; Central Nervous System Stimulants; Corpus Striatum; Dynorphins; Gene Expression Regulation; In Situ Hybridization; Male; Microinjections; Motor Activity; Neurokinin-1 Receptor Antagonists; Neuropeptides; Protein Precursors; Rats; Rats, Sprague-Dawley; RNA, Messenger; Seizures; Sleep; Substance P