Dopamine receptor agonists modulate voluntary alcohol intake independently of individual levels of alcohol intake in rats

Abstract

Rationale: Individual susceptibility to alcohol use disorder has been related to functional changes in dopaminergic neurotransmission.

Objectives: The aim of the current work was to assess the effects of selective dopamine D1 and D2 receptor agonists and antagonists on alcohol consumption in rats that differ in individual levels of alcohol intake.

Methods: The effects of the dopamine D1 receptor agonist SKF 82958, the dopamine D1 receptor antagonist SCH 23390, the dopamine D2 receptor agonist sumanirole and the dopamine D2 receptor antagonist L741,626 on alcohol consumption and preference were assessed at different time points after treatment in subgroups of low and high alcohol drinking rats (LD and HD) using an intermittent alcohol access paradigm.

Results: SKF 82958 decreased alcohol intake and alcohol preference throughout the 24-h session. Sumanirole decreased alcohol intake during the first 2 h, but increased alcohol intake during the remainder of the session. The effects of SKF 82958 and sumanirole on alcohol intake and alcohol preference were comparable in LD and HD. By contrast, the dopamine receptor antagonists SCH 23390 and L741,626 did not alter alcohol consumption in either group at any time point.

Conclusions: These data indicate that stimulation of dopamine D1 receptors reduces alcohol intake, but that endogenous dopamine does not play a primary role in alcohol consumption. Moreover, the difference in alcohol consumption between LD and HD does not involve altered dopamine signaling.

Keywords: Addiction; Alcohol; Dopamine receptor; Individual differences.

Fig. 1

The effects of the dopamine D1 receptor agonist SKF 82958 and the dopamine D1 receptor antagonist SCH 23390 on alcohol intake and preference in HD and LD. SKF 82958 decreased alcohol intake and preference during the entire session to a similar extent in HD and LD (a, b). SCH 23390 did not alter alcohol intake (c). Alcohol preference was affected by SCH 23390 but post hoc analyses did not reveal significant differences from vehicle for any of the doses tested (d). HD consumed more alcohol than LD (with a near significant trend for SKF 82958): SKF 82958: F _{(1,10) group} = 4.83, p = 0.053, SKF 82958: F _{(1,12) time x group} = 4.88, p < 0.05; SCH 23390: F _{(1,10) group} = 16.09, p < 0.003, SCH 23390: F _{(1,14) time x group} = 17.62, p < 0.001. The preference for alcohol was also higher for HD compared to LD and was independent of session time (with a near significant trend for SKF 82958): SKF 82958: F _{(1,10) group} = 4.74, p = 0.055; SCH 23390: F _{(1,10) group} = 17.11, p < 0.003. Data are presented as the mean + SEM. The effect of SKF 82958 did not interact with the session time. Therefore, the asterisk reflects the overall differences from vehicle in post hoc pairwise comparisons (p < 0.05)

Fig. 2

The effects of the dopamine D2 receptor agonist sumanirole and the dopamine D2 receptor antagonist L741,626 on alcohol intake and preference in HD and LD. Sumanirole decreased alcohol intake after 2 h of alcohol exposure in both groups, without affecting alcohol intake after 7 or 24 h of alcohol exposure (a). Sumanirole had no effect on the preference for alcohol (b). L741,626 did not affect alcohol intake and preference (c, d). HD consumed more alcohol than LD: Sumanirole: F _{(1,30) group} = 27.34, p < 0.001, F _{(1,35) time x group} = 29.78, p < 0.001; L741,626: F _{(1,30) group} = 38.51, p < 0.001, F _{(1,37) time x group} = 40.19, p < 0.001. The preference for alcohol was also higher for HD compared to LD and was independent of session time: Sumanirole: F _{(1,29) group} = 12.21, p < 0.003; L741,626: F _{(1,30) group} = 22.36, p < 0.001. Data are presented as the mean + SEM. Asterisk means different from vehicle in post hoc pairwise comparisons (p < 0.05)

Fig. 3

Replication of the effects of the highest dose of the dopamine D2 receptor agonist sumanirole and the dopamine D2 receptor antagonist L741,626 on alcohol intake and preference in HD and LD. Sumanirole decreased alcohol intake in both groups after 2 and 7 h of alcohol exposure, but was without effect after 24 h of alcohol exposure (a). Sumanirole decreased the preference for alcohol after 2 h of alcohol exposure but had no effects after 7 and 24 h of alcohol exposure (b). L741,626 did not affect alcohol intake and preference (c, d). HD consumed more alcohol than LD: Sumanirole: F _{(1,10) group} = 11.36, p < 0.008, F _{(1,13) time x group} = 11.80, p < 0.004; L741,626: F _{(1,10) group} = 5.82, p < 0.04, F _{(1,13) time x group} = 1.68, n.s. There were near significant trends for a higher preference for alcohol in HD compared to LD, and the preference was independent of session time: Sumanirole: F _{(1,10) group} = 4.03, p = 0.073; L741,626: F _{(1,9) group} = 4.51, p = 0.063. Data are presented as the mean + SEM. Asterisk means different from vehicle in post hoc pairwise comparisons (p < 0.05)