Adaptive changes occur in response to repeated exposure to drugs.
Although ethanol (EtOH) is known to induce pharmacokinetic tolerance, the
effects of EtOH on in vivo, magnetic resonance (MR)-detectable
brain measures across repeated exposures have not previously been reported. Of
28 rats weighing 341±22g at baseline, 15 were assigned to the EtOH group
and 13 to the control (Ctrl) group. EtOH animals were exposed to 5 cycles of
4-days of EtOH treatment followed by 10 days of recovery. Rats in both groups
had structural MR imaging (MRI) scans and whole brain MR spectroscopy (MRS) at
baseline, immediately following each binge period, and after each recovery
period (total=11 MR scans per rat).
Average blood alcohol levels (BALs) across each of the 5, 4-day binge
periods were 298, 300, 301, 312, 318 mg/dL. Cerebrospinal fluid (CSF) volumes of
the lateral ventricles and cisterns showed enlargement with each binge EtOH
exposure but recovery with each abstinence period. Similarly, changes to MRS
metabolites were transient: levels of N-acetyl aspartate (NAA) and total
creatine (tCr) decreased, while those of choline-containing compounds (Cho) and
glutamate/glutamine (Glx) increased with each binge EtOH exposure cycle, but
also recovered during each abstinence period. The directionality of changes in
response to EtOH were in expected directions based on previous, single-binge
EtOH exposure experiments, but the current results do not provide support for
accruing pathology with repeated binge EtOH exposure.