Jacobian Mapping Reveals Converging Brain Substrates of Disruption and Repair in Response to Ethanol Exposure and Abstinence in 2 Strains of Rats

Background In a previous study using Jacobian mapping to evaluate the morphological effects on the brain of binge (4-day) intragastric ethanol (EtOH) on wild-type Wistar rats, we reported reversible thalamic shrinkage and lateral ventricular enlargement, but persistent superior and inferior colliculi shrinkage in response to binge EtOH treatment. Methods Herein, we used similar voxel-based comparisons of Magnetic Resonance Images collected in EtOH-exposed relative to control animals to test the hypothesis that regardless of the intoxication protocol or the rat strain, the hippocampi, thalami, and colliculi would be affected. Results Two experiments [binge (4-day) intragastric EtOH in Fisher 344 rats and chronic (1-month) vaporized EtOH in Wistar rats] showed similarly affected brain regions including retrosplenial and cingulate cortices, dorsal hippocampi, central and ventroposterior thalami, superior and inferior colliculi, periaqueductal gray, and corpus callosum. While most of these regions showed significant recovery, volumes of the colliculi and periaqueductal gray continued to show response to each proximal EtOH exposure but at diminished levels with repeated cycles. Conclusions Given the high metabolic rate of these enduringly affected regions, the current findings suggest that EtOH per se may affect cellular respiration leading to brain volume deficits. Further, responsivity greatly diminished likely reflecting neuroadaptation to repeated alcohol exposure. In summary, this unbiased, in vivo-based approach demonstrating convergent brain systems responsive to 2 EtOH exposure protocols in 2 rat strains highlights regions that warrant further investigation in both animal models of alcoholism and in humans with alcohol use disorder.

Automated summary

In two experiments with different intoxication protocols and rat strains, regions including retrosplenial and cingulate cortices, dorsal hippocampi, central and ventroposterior thalami, superior and inferior colliculi, periaqueductal gray, and corpus callosum were affected. Although most regions showed significant recovery, volumes of the colliculi and periaqueductal gray continued to respond to each proximal EtOH exposure with repeated cycles, likely due to diminished responsivity reflecting neuroadaptation to repeated alcohol exposure. These findings suggest that EtOH exposure may affect cellular respiration leading to brain volume deficits, with regions such as the colliculi and periaqueductal gray showing enduring effects.