Developing a reverse translational model of low-intensity rTMS in alcohol use disorder: The influence of theta burst stimulation protocols on binge alcohol drinking in mice.

BACKGROUND

Repetitive Transcranial Magnetic Stimulation (rTMS) is a promising treatment tool for Alcohol Use Disorder (AUD). A challenge facing the field is that the optimal TMS parameters to reduce drinking are unknown. There are now rodent TMS coils which can be adapted to evaluate rTMS-induced changes in alcohol consumption in a rapid, cost-effective manner.

OBJECTIVE

Develop a preclinical model of rTMS in alcohol consuming rodents and collect pilot data to evaluate the influence rTMS parameters (here, theta burst pattern) on change in alcohol consumption and biochemistry.

METHODS

66 C57BL/6 J mice (32 F) received sham, intermittent Theta Burst Stimulation (iTBS), or continuous Theta Burst Stimulation (cTBS) (14 sessions, 2 sessions/day, low intensity 16mT stimulation). Alcohol consumption and preference were evaluated before and after rTMS using a two-bottle choice, Drinking in the Dark (DID) paradigm. Cortical brain tissue was assayed for BDNF gene expression via qPCR. During DID sessions, control mice (n = 31) were given access to water only.

RESULTS

Relative to sham, iTBS increased alcohol consumption (d=0.72) and preference (d=0.44), however these results were not statistically significant. Female mice receiving iTBS, experienced a significant, large increase in alcohol consumption (p = 0.02, d=1.5). Among water only mice, iTBS (d=-1.01) and cTBS (d=-1.03) significantly reduced BDNF expression.

CONCLUSIONS

This preclinical model is a feasible method to evaluate rTMS-induced changes in alcohol consumption. This pilot analysis warrants future work evaluating the influence of rTMS parameters and sex on changes in drinking or drug-seeking behaviors.