Fig. 2: Nicotine and ethanol induce similar response profiles across two VTA DA pathways.
a In vivo juxtacellular recordings were performed following retrobead injections into either the nucleus accumbens (NAc: lateral shell, medial shell, core) or the amygdala (Amg: basolateral and central nuclei). VTA dopamine (DA) neurons responding to i.v. ethanol (EtOH; 250 mg/kg) or nicotine (Nic; 30 µg/kg) were identified post hoc via immunofluorescence for tyrosine hydroxylase (TH), neurobiotin (NB), and retrobeads (RB). Scale bar: 20 µm. b Distribution of nicotine-evoked firing rate changes (% of baseline) in NAc- (brown, n = 13) and Amg-projecting (purple, n = 16) DA neurons (Kolmogorov-Smirnov test: D = 0.86, ***p = 8.4e-06). c Left: proportion and individual firing rate variation from baseline of activated/inhibited NAc-projecting DA neurons after nicotine (Wilcoxon test: V = 80, **p = 0.01). Right: same for Amg-projecting neurons (V = 11, **p = 0.002). d Mean time course of normalized firing frequency after nicotine in activated NAc-projecting (top, n = 12) and inhibited Amg-projecting (bottom, n = 15) neurons, compared to saline (Maximum of % variation, t-test: NAc-proj, t11 = 4.58, ***p = 0.0007; Amg-proj, t13 = −6.26, ***p = 2.9e-05). e, f Same analyses as in (b, c) after ethanol. Ethanol-induced firing rate changes were significantly different between NAc- and Amg-projecting DA neurons (Kolmogorov-Smirnov test: D = 0.66, **p = 0.002). g same as (d) for ethanol in activated NAc-projecting (top, n = 11) and inhibited Amg-projecting (bottom, n = 13) DA neurons (Maximum of % variation, t-test: NAc-proj, t11 = 4.83, ***p = 0.0005; Amg-proj, t12 = −2.34, *p = 0.04). h Ethanol- and nicotine-induced responses were significantly correlated across all DA neurons (Pearson’s correlation: t27 = 4.15, R = 0.62, ***p = 0.0003). Correlated (filled dots) and uncorrelated (empty dots) responses are shown for NAc- (n = 12/1) and Amg-projecting (n = 14/2) neurons. Data are presented as mean ± SEM. All statistical tests are two-sided.
