DOPAMINE (DA) D2 CLASS RECEPTORS (D2R) MEDIATE EXCITABILITY OF RAT NUCLEUS ACCUMBENS (NAC) NEURONS VIA REGULATING ACTIVITY OF DIFFERENT TYPES OF ION CHANNELS AND SIGNALING PATHWAYS

PEREZ MF, HU X.-T, WHITE FJ

Washington, USA

Congreso; Society for Neuroscience; 2005

Society for Neuroscience

The NAc is a critical forebrain region in the reward system which regulates many aspects of drug addiction. The neuronal activity in the NAc is mediated by DA receptors. Although DA signaling has received considerable attention, the mechanism underlying D2R mediation of the NAc activity is still ambiguous. Our recent findings indicate that D2R stimulation reduces evoked Na⁺ spikes, and this effect of D2R on NAc activity is reversed by block of A-type K⁺ currents (I_A). However, it is unknown if other types of ion channels also participate in D2R-mediated change in NAc excitability.

In this study we performed visualized whole-cell current-clamp recordings in brain slices to determine whether D2R stimulation alters activity of inwardly rectifying K⁺ currents (IRKCs) and high voltage activated (HVA-) Ca²⁺ currents in medium spiny neurons located in the core NAc. Our results reveal that D2R-induced decrease in Na⁺ spikes (by quinpirole, 10 mM) was mimicked and occluded by inhibition of PKA. D2R stimulation also depolarized resting membrane potential (RMP), decreased firing threshold, attenuated afterhyperpolarization, and reduced inward rectification during membrane hyperpolarization. Moreover, it also decreased the amplitude and duration of HVA-Ca²⁺ plateau potentials. The D2R effects on Ca²⁺ channels were mimicked and occluded by block of L-type Ca²⁺ channels (nifedipine, 5 mM). These findings suggest that D2R-induced decrease in firing of NAc neurons is an integrated result of ion channel modulation, which should be attributed to at least increased I_A (likely via facilitating Ca²⁺ release with inhibition of PKA), and decreased I_Ca influx with enhanced dephosphorylation of the L channel. They also suggest that D2R mediation decreases both K⁺ efflux at the RMP and K⁺ influx during membrane hyperpolarization, which lead to depolarization of RMP and attenuation of IRKCs, respectively.