Figure 4.

μ-Opioids modulate DA responses by inhibiting cholinergic interneuron activity. a, A saturating concentration of EM-1 (1 μm) occludes further modulation of DA overflow by nicotine. Peak DA responses elicited by single pulses or, where labeled, 25 Hz burst stimuli showing that nicotine (1 μm) is not effective in modulating evoked DA overflow when applied subsequent to EM-1. b, On-cell electrophysiological recordings revealed that EM-1 (1 μm) suppresses the firing rate of cholinergic interneurons in the NAc shell hotspot region (n = 6). Frequency data from each cell was normalized to baseline for averaging (average baseline firing rate, 3.9 ± 1.7 Hz). c, An example whole-cell recording from a cholinergic interneuron in the NAc shell hotspot region before and after a 2 min bath application of 1 μm EM-1. d, Whole-cell voltage-clamp recordings from cholinergic interneurons in the NAc shell hotpot region reveal that EM-1 produces an outward current. Top, Example trace from a single cell. Bottom, Summary data (n = 5). e, Voltage ramps from −120 to −60 mV were applied during current response to EM-1 in cholinergic interneurons from the NAc shell hotspot. Currents were averaged and the difference current was obtained by subtracting control from EM-1 to produce the current–voltage relationship for each cell. The largest inward current was normalized to −1 and the traces were averaged across all cells. The reversal potential (−104 ± 10 mV) was similar to calculated Nernst potential for potassium (−107 mV; n = 5).