Dopamine D 2-class receptor supersensitivity as reflected in Ca 2+ current modulation in neostriatal neurons

Abstract

The loss of dopaminergic neurons followed by dopamine (DA) depletion in the neostriatum is a hallmark of Parkinson's disease. Among other changes, DA D 2-receptor class (D 2R-class) supersensitivity is a result of striatal DA depletion. Pharmacological, biochemical and behavioral data have documented this phenomenon, but clear electrophysiological-functional correlates are still lacking. This work describes an electrophysiological correlate of D 2R-class supersensitivity in DA-depleted striata after unilateral 6-hydroxydopamine (6-OHDA) lesions in the rat substantia nigra compacta (SNc). Ca 2+ current modulation mediated by D 2R-class activation reflected an altered sensitivity. Thus, while the concentration–response relationship (C–R plot) from control striata was better fit with a two sites model, the C–R plot obtained from DA-depleted striata was better fit by a three sites model, exhibited a considerable leftward shift, and presented an increased maximal response. Because Ca 2+ current modulation by D 2R-class activation is involved in the control of spiny neurons excitability and their synaptic GABA release, the present findings may help to explain several functional changes found in the striatal circuitry after dopaminergic denervation.