TRPV1 agonist capsaicin induces a stronger potentiation of glutamate transmission and firing in lateral habenula neurons from ethanol naive rats. Representative traces showing enhancement of spontaneous excitatory postsynaptic currents induced by 3 µM capsaicin in lateral habenula neurons from a Naive (A1) or an ethanol-withdrawn (EtOH-WD; B1) rat. (A2 and B2) Exemplar current traces were acquired in A1 and B1, before and during capsaicin application. Cumulative probability plots show higher incidence of events with shorter inter-event interval, and amplitude before and after capsaicin application in the lateral habenula neurons of Naive (A3) and EtOH-WD (B3) rats (Kolmogorov-Smirnov test). Capsaicin elicited a concentration-dependent increase in spontaneous excitatory postsynaptic current frequency (C), which was significantly greater in Naïve than in EtOH-WD neurons. The smooth curve is the best fit to the data by the logistic equation. Capsaicin did not significantly alter the mean spontaneous excitatory postsynaptic current (sEPSC) amplitude (D). (E) A representative example of increased spontaneous firing rate induced by 3 µM capsaicin in a Naïve or an ethanol-withdrawn neuron. (F) Capsaicin caused a concentration-dependent increase in firing rate, which was significantly greater in the Naïve than the EtOH-WD neurons. *P < 0.05, **P < 0.01, ***P < 0.001 relative to 0.01 μM capsaicin; ^###P < 0.001, Naïve in comparison with EtOH-WD rats. ^{^}P < 0.05, ^{^^}P < 0.01, ^{^^^}P < 0.001, Naïve in comparison with EtOH-WD rats that underwent the same dose of capsaicin. Data were analyzed with two-way ANOVA and Tukey post hoc comparison. aCSF, artificial cerebrospinal fluid.