Minocycline reduces ethanol drinking

Abstract

Alcoholism is a disease characterized by continued alcohol consumption despite recurring negative consequences. Thus, medications that reduce the drive to consume alcohol can be beneficial in treating alcoholism. The neurobiological systems that regulate alcohol consumption are complex and not fully understood. Currently, medications are available to treat alcoholism that act either by causing accumulation of a toxic metabolite of ethanol, or by targeting specific transmitter receptors. The purpose of our study was to investigate a new potential therapeutic pathway, neuroimmune interactions, for effects on ethanol consumption. We hypothesized that neuroimmune activity of brain glia may have a role in drinking. We utilized minocycline, a second generation tetracycline antibiotic that has immune modulatory actions, to test our hypothesis because it is known to suppress microglia, and to a lesser extent astroglia, activity following many types of insults to the brain. Treatment with 50mg/kg minocycline significantly reduced ethanol intake in male and female C57Bl/6J mice using a free choice voluntary drinking model. Saline injections did not alter ethanol intake. Minocycline had little effect on water intake or body weight change. The underlying mechanism whereby minocycline reduced ethanol intake requires further study. The results suggest that drugs that alter neuroimmune pathways may represent a new approach to developing additional therapies to treat alcoholism.

Figure 1

Minocycline, but not saline, reduces ethanol intake in male (A) and female (B) C57Bl/6J mice. The bars represent average ethanol consumption in g/kg over the four days of measurement as mean ± SEM. Saline injection had no effect on ethanol intake (p > 0.05, n=10 per group). Repeated measures one-way ANOVA revealed a significant minocycline treatment effect for the male (p< 0.0001, n=14) and female mice (p< 0.0001, n=13). Tukey’s post-hoc analysis revealed significant differences among experimental phases as depicted. (*** p< 0.0001, ** p< 0.001, and * p < 0.01). Inserts: Body weight data (mean ± SD) during experimentation with minocycline is shown about each graph for male and female mice.

Figure 2

Effects of minocycline on water intake in male (A) and female (B) C57Bl/6J mice. The bars represent average water consumption in g/kg over the four days represented as mean ± SEM for n=14 for the male and n=13 for female mice for the different experimental phases denoted on the abscissa. Repeated measures one-way ANOVA revealed a significant treatment effect only for the male (p< 0.001) mice whereas treatment had no significant effect on female mice (p = ns). Tukey’s post-hoc analysis among experimental phases in male mice revealed statistically significant difference as depicted. (** p< 0.001, and * p< 0.01).