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. Author manuscript; available in PMC: 2017 Oct 19.
Published in final edited form as: Neuron. 2016 Oct 6;92(2):493–504. doi: 10.1016/j.neuron.2016.09.029

Figure 6. Stress Requires Excitatory GABA Shift to Attenuate Ethanol-induced DA Levels and Increase Ethanol Self-administration Ex Vivo and In Vivo.

Figure 6

A) In the presence of bath applied acetazolamide (ACTZ), ethanol-induced VTA GABA neuron firing was no longer enhanced after exposure to stress (red) and was similar to the response of the unstressed controls (black). The effect of stress exposure and ethanol application in the absence of acetazolamide from Figure 4D is shown for comparison (dotted red line), n = 8 cells/group. Note, bath application of acetazolamide on VTA slices (before ethanol) did not produce any significant alterations in the mean basal firing rate of GABA neurons between control and stress groups.

B) In the presence of bath ACTZ, ethanol-induced VTA DA neuron firing was no longer attenuated after exposure to stress (red) and was similar to the response of the unstressed controls (black). The effect of stress exposure and ethanol application in the absence of ACTZ from Figure 3D is shown for comparison (dotted red line), n = 10–14 cells/group. Note, bath application of ACTZ on VTA slices (before ethanol) did not produce any significant alterations in the mean basal firing rate of DA neurons between control and stress groups.

C) Stressed animals received intra-VTA infusion of ACTZ or vehicle prior to the onset of baseline microdialysis sample collection. Subsequent ethanol-induced DA release in the NAc was measured.

D) In contrast to vehicle injection (red), ethanol-induced DA levels in the NAc following ACTZ infusion were not blunted (blue) and were similar to the control response from Figure 2B (dotted black line). **Significantly different from the VTA vehicle group by ANOVA with repeated measure, p < 0.01, n = 7 rats/group.

E) Stressed animals received bilateral intra-VTA infusions of ACTZ or vehicle prior to the onset of each self-administration session.

F) ACTZ-infused stressed animals consumed significantly less ethanol (blue) compared to vehicle-infused stressed animals (red). Ethanol consumption in unstressed control rats from Figure 1C is shown for comparison (dotted horizontal line). *Significantly different from the VTA vehicle group by t-test, p < 0.05, n = 10–14 rats/group.