Influence of potassium concentration in microdialysis perfusate on basal and stimulated striatal dopamine release: effect of ceruletide, a cholecystokinin-related peptide.

Abstract

The in vivo microdialysis method was used to study the effect of the cholecystokinin-related peptide, ceruletide, on extracellular levels of dopamine (DA) in the striatum following perfusion with various K+ concentrations. Increasing the K+ concentration in the perfusate from 4 to 15 or 17.5 mM did not change basal DA release or release evoked by electrical stimulation of the medial forebrain bundle (MFB). However, when the perfusing solution contained 20 or 30 mM K+, dose-dependent reductions of both basal and MFB-stimulated DA release occurred. Subcutaneous administration of ceruletide at 160 micrograms/kg had no influence on the basal or MFB-stimulated DA release with 4 or 15 mM K+ in the perfusate. However, after perfusion with 17.5 mM K+, ceruletide significantly attenuated the basal and MFB-stimulated DA release. Carbachol (10 microM) locally applied via the dialysis probe also attenuated MFB-stimulated DA release after perfusion with 17.5 mM K+. From these results, we conclude that under appropriate depolarization of striatal DA terminals, ceruletide induces further depolarization and inactivation of nigrostriatal DA terminals. The present data suggest that this effect may be mediated via intrinsic cholinergic neurons in the striatum.