DOPAMINE D2 RECEPTOR-MEDIATED POTASSIUM CURRENTS REGULATE EXCITABILITY OF RAT NUCLEUS ACCUMBENS NEURONS AT DIFFERENT MEMBRANE POTENTIALS

MARIELA F. PÉREZ.; WHITE FJ; XIU-TI HU

JOURNAL OF NEUROPHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Lugar: Bethesda; Año: 2006 vol. 96 p. 2217 - 2228

0022-3077

The nucleus accumbens (NAc) is a forebrain area in the mesocorticolimbic dopamine (DA) system that regulates many aspects of drug addiction. Neuronal activity in the NAc is modulated by different subtypes of DA receptors. Although DA signaling has received considerable attention, the mechanisms underlying D(2)-class receptor (D(2)R) modulation of firing in medium spiny neurons (MSNs) localized within the NAc remain ambiguous. In the present study, we performed whole cell current-clamp recordings in rat brain slices to determine whether and how D(2)R modulation of K(+) channel activity regulates the intrinsic excitability of NAc neurons in the core region. D(2)R stimulation by quinpirole or DA significantly and dose-dependently decreased evoked Na(+) spikes. This D(2)R effect on inhibiting evoked firing was abolished by antagonism of D(2)Rs, reversed by blockade of voltage-sensitive, slowly inactivating A-type K(+) currents (I(As)), or eliminated by holding membrane potentials at levels in which I(As) was inactivated. It was also mimicked by inhibition of cAMP-dependent protein kinase (PKA) activity, but not phosphatidylinositol-specific phospholipase C (PI-PLC) activity. Moreover, D(2)R stimulation also reduced the inward rectification and depolarized the resting membrane potentials (RMPs) by decreasing "leak" K(+) currents. However, the D(2)R effects on inward rectification and RMP were blocked by inhibition of PI-PLC, but not PKA activity. These findings indicate that, with facilitated intracellular Ca(2+) release and activation of the D(2)R/G(q)/PLC/PIP(2) pathway, the D(2)R-modulated changes in the NAc excitability are dynamically regulated and integrated by multiple K(+) currents, including but are not limited to I(As), inwardly rectifying K(+) currents (I(Kir)), and "leak" currents (I(K-2P)).