Fig. 5: Chronic drinking drove persistent upregulation of kappa opioid receptor control of dopamine release and altered function-transcription relationships.
A Representative dopamine release (1 µM U50,488). B U50,488 decreased dopamine release to a greater extent in drinkers (repeated measures two-way ANOVA; dose: F1, 14 = 79.28, p < 0.0001; group: F1, 14 = 4.81, p < 0.05; dose x group: F1, 14 = 0.01, p = 0.91). C BaCl2 increased dopamine release to a greater extent in drinkers (unpaired t-test; t5 = 3.41, p = 0.02; controls: n = 3, drinkers: n = 4). D Nalfurafine decreased dopamine release in both groups (two-way ANOVA; concentration: F1, 6 = 30.76, p = 0.0015; group: F1, 6 = 0.10, p = 0.76; concentration x group: F1, 6 = 0.75, p = 0.42; Šídák’s test: baseline vs. nalfurafine; controls: t6 = 4.06, p = 0.01, n = 3; drinkers: t6 = 3.82, p = 0.02, n = 5). E–O Best-fit linear regression. Inset: Pearson’s r and p-values. E Change in dopamine release by U50,488 (300 nM) was correlated with OPRK1 expression in drinkers, not controls. F U50,488 potency was not correlated with PDYN, (G) ARRB1, or (H) ARRB2 expression in either group. I There was no association between OPRK1 expression and efficacy of 1 µM U50,488 in controls. J Efficacy was not associated with PDYN or (K) ARRB1 in either group. L ARRB2 and efficacy were not correlated in controls, but negatively correlated in drinkers. M Mean slope of the regressions was greater in controls (unpaired t-test; t14 = 3.08, p = 0.008). The mean slope for controls (one sample t-test; t7 = 3.45, p = 0.01), but not drinkers (one sample t-test; t7 = 1.52, p = 0.17), was greater than zero. N In controls, ranked expression was positively correlated with rank sensitivity. O This association was reversed in drinkers. All statistical tests were two-tailed. Unless otherwise indicated, values indicate mean ± SEM. (*p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001, †p ≤ 0.05 vs 0) (unless otherwise noted, controls: n = 8; drinkers: n = 8).
