receptor modulation of K ϩ channel activity regulates excitability of nucleus accumbens neurons at different membrane potentials. J Neurophysiol 96: 2217-2228, 2006. First published August 2, 2006 doi:10.1152/jn.00254.2006. 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 ϩ 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 ϩ 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 ϩ 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 ϩ 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 2ϩ 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 ϩ currents, including but are not limited to I As , inwardly rectifying K ϩ currents (I Kir ), and "leak" currents (I K-2P ).

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Photoinduced antibacterial gold nanoparticles were developed as an alternative for the treatment of antibiotic-resistant bacteria. Thanks to the amoxicillin coating, they possess high in vivo stability, selectivity for the bacteria wall, a good renal clearance, and are completely nontoxic for eukaryotic cells at the bactericidal concentrations. A simple one-step synthesis of amoxi@AuNP is described at mild temperatures using the antibiotic as both reducing and stabilizing agent. Time-resolved fluorescence microscopy proved these novel nano-photosensitizers, with improved selectivity, are bactericidal but showing excellent biocompatibility toward eukaryotic cells at the same dose (1.5 μg/mL) when co-cultures are analyzed. Their stability in biological media, hemocompatibility, and photo-antibacterial effect against sensitive and antibiotic-resistant Staphylococcus aureus were evaluated in vitro, whereas toxicity, renal clearance, and biodistribution were studied in vivo in male Wistar rats. The use of these nanoparticles to treat antibiotic-resistant infections is promising given their high stability and cytocompatibility.

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