Kinetics and Geometry of the Excitatory Dopaminergic Transmission in the Rat Striatum in Vivo

Abstract

Dopamine release in NACC can be reproducibly evoked by chemical stimulation of dopaminergic cell bodies using N-methyl-D-aspartate (NMDA) microinjection in the ventral tegmental area (VTA). In fact, when NMDA (65 nl, 00 μM) was pressure-injected in the core of the VTA, the discharge activity of dopaminergic neurons was strongly enhanced for 3-4 min with a maximum 30 to 60 sec after injection. The kinetics of this increase closely paralleled that of the discharge activity of dopaminergic neurons. In a recent study, the effects of these NMDA injections in VTA on the discharge activity of 182 single neurons in NACC were investigated. Among them, 142 were strongly excited: Their mean discharge rate was more than doubled during the 2 min that followed NMDA injection. The excitatory effects were actually because of the dopamine overflow evoked in NACC by NMDA injection in VTA. Both neuronal excitation and evoked dopamine release exhibited the same time course and the same geometry: When the NMDA pipette was raised 0.75 mm above the core of the VTA, both effects vanished. When dopaminergic neurons were previously lesioned with 6-hydroxydopamine, NMDA injections were no longer effective. It was observed that systemic administration of the D1 antagonist SCH 23390 (0.25 mg/kg s.c.) completely blocked the excitatory responses of all 15 neurons tested but did not affect the evoked dopamine overflow. is a good correlation between the amplitude of the dopamine overflow and that of the excitatory response. This is also true concerning the effects of MFB electrical stimulations: Both overflow and excitations are positively correlated with the number of stimulation pulses.