An in vivo voltammetric characterization of the uptake of catecholamines in the medial prefrontal cortex and striatum of the rat.

摘要

A novel method of in vivo chronoamperometry is presented in which carbon fiber microelectrodes are used to measure the kinetics of catecholamine uptake by the dopamine transporter. A carbon electrode is placed less than 400 {dollar}mu{dollar}m from the tip of a 1.0 {dollar}mu{dollar}L syringe which is used to administer a rapid pulse of dopamine or other catecholamine in physiological buffer during an experiment. A spherical-source diffusion model modified for diffusion of substances in brain tissue is used to remove diffusion from the resulting concentration-time profiles, yielding isolated kinetics of uptake by the transporter. The method controls the composition of the sampled region so that it is possible to determine the dependence of catecholamine transport upon Na{dollar}sp+{dollar} and Cl{dollar}sp-{dollar} in vivo for the first time via the replacement of these ions in the physiological buffer ejected from the syringe and verification of ion concentrations with ion selective microelectrode measurements. In addition to studies in the striatum which investigate the pharmacology and structure-activity of the dopamine transporter, studies are also presented which investigate the effect of repeated cocaine treatments followed by three weeks of withdrawal on the kinetic uptake of dopamine in the striatum and the effect of an acute dose of cocaine after such treatments. The results of experiments conducted in the medial prefrontal cortex are also presented in which the pharmacology and structure-activity relationships were investigated so that comparisons of the kinetic function of the dopamine transporter may be made between the two regions of the brain.