Nitric oxide (NO) signaling plays an important role in locomotor activity and the behavioral and sensitizing effects of various psychoactive drugs.  The current study examined the impact of exogenous NO on the membrane properties and excitability of medium spiny neurons (MSNs) within the core of the nucleus accumbens (NAc).  Whole-cell current clamp recordings were made in rat brain slice preparations prior to and during bath application (3-10 min) of the NO generator S-nitroso-N-acetylpenicillamine (SNAP, 500 nM).  SNAP perfusion (3 min) did not initially affect the resting membrane potential (RMP) or input resistance of MSNs (p>0.05, paired t-test, n=10 cells, 6 rats).  SNAP application (3 min) did, however, induce significant decreases in inward rectification during membrane hyperpolarization and sodium spike activity evoked by depolarizing current steps (p<0.05, RM-ANOVA).  SNAP perfusion also induced a significant decrease in the slope and an increase in the duration of evoked action potentials (p<0.05).  The effects of SNAP on action potential duration and evoked firing activity returned to control levels after 10 min of drug application.  Moreover, a significant hyperpolarization in RMP, decrease in action potential amplitude, and further reduction in slope were observed 10 min after SNAP administration (p<0.05).  These findings suggest that acute activation of NO signaling in the NAc core may depress spike activity evoked from RMP by decreasing Na+ channel activity and increasing voltage-gated K+ currents.  These acute effects of exogenous NO appear to be transient, whereas, prolonged NO signaling may produce enduring changes in Na+ channels and inward-rectifying K+ channels, including those active at RMP.  Studies are underway to determine whether these effects involve cGMP signaling pathways or direct actions of NO on channel proteins via S-nitrosylation.