clozapine and senktide

The regulation of tachykinin-evoked acetylcholine release by the dopaminergic system in the neostriatum was examined. We studied the effect of selective and potent tachykinin agonists for each subtype of receptor ([Sar9,Met(O2)11]-Substance P for NK1; [Nle10]-Neurokinin A4-10 for NK2; and senktide for NK3) on endogenous acetylcholine release from rat striatal slices where the dopaminergic system was modified either by 6-hydroxydopamine lesion or by dopamine receptor antagonists. Unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway induced a decrease in senktide-evoked acetylcholine release and an increase in the effect of [Nle10]-Neurokinin A4-10. The same results were obtained after chronic haloperidol treatment, whereas SCH-23390 or clozapine treatment had no effect on tachykinin-evoked acetylcholine release, suggesting an involvement of D2 receptors. 6-hydroxydopamine lesion induced a diminution in the density of NK3 receptor, which could be related to the reduction in senktide-evoked acetylcholine release.

Topics: Acetylcholine; Animals; Benzazepines; Clozapine; Dopamine; Dopamine Agents; Haloperidol; In Vitro Techniques; Male; Neostriatum; Neurons; Oxidopamine; Peptide Fragments; Rats; Rats, Sprague-Dawley; Receptors, Neurokinin-3; Substance P; Tachykinins