Transient CNS responses to repeated binge ethanol treatment

Abstract

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.

Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: Relationships to resting-state functional connectivity

“…For example, following short-term administrations of cocaine (Li et al, 2012) or alcohol (Zahr et al, 2015), rats showed transient striatal (Li et al, 2012) or whole-brain (Zahr et al, 2015) increases in glutamate and/or GABA [but see (Lee et al, 2014)]. Such results are consistent with the idea that addiction-related decreases in glutamate or GABA could reflect neuroadaptations to chronic drug exposure.…”

Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo

“…Although the TE group did not show statistically significant group effects, lateral ventricle and total CSF volumes were enlarged following the first EtOH exposure period. Unlike our repeated EtOH exposure experiment (Zahr et al 2015b), however, there was a relatively suppressed effect of the second EtOH exposure on lateral ventricular volume in the TE group. One potential explanation for the attenuated effect of the second EtOH treatment is that these EtOH-exposed animals were being given daily injections of thiamine.…”

“…Animal models can be used to distinguish components of the processes associated with damage to the brain in response to alcohol exposure (Pfefferbaum et al 2008; Zahr et al 2010b; Zahr et al 2014b; Zahr et al 2013; Zahr et al 2009b; Zahr et al 2015b). Our in vivo magnetic resonance imaging (MRI) studies of rats have consistently shown increases in cerebrospinal fluid (CSF) volumes following ethanol (EtOH) exposure.…”

“…With repeated EtOH (i.g.) exposure, changes in metabolite levels did not accrue: levels of NAA decreased, while those of Cho increased with each EtOH exposure cycle, but then recovered during each abstinence period (Zahr et al 2015b). Although these EtOH exposure studies were informative, they did not fully model the persistent ventricular enlargement seen in chronic alcoholism in humans (Pfefferbaum et al 2012; Rosenbloom et al 2010) nor the low levels of NAA (frontal regions: Bendszus et al 2001; Durazzo et al 2004; Durazzo et al 2010; Fein et al 1994; Jagannathan et al 1996; Parks et al 2002; Schweinsburg et al 2003; Seitz et al 1999) and Cho (Bendszus et al 2001; Durazzo et al 2004; frontal regions: Ende et al 2005; Fein et al 1994; Parks et al 2002; cerebellar regions: Seitz et al 1999) observed in recently sober alcoholics relative to healthy controls.…”

Recherche translationnelle sur les troubles cognitifs et comportementaux dans les maladies neurologiques et psychiatriques

“…Les développements techniques en informatique et e-santé permettent d'envisager de nouvelles méthodes de monitoring de la consommation d'alcool chez les patients, en utilisant par exemple des applications Smartphone [42]. De manière complémentaire, les études conduites chez l'animal permettent de modéliser les différents profils d'évolution des consommations (abstinence totale, binge, consommation faible mais régulière) et permettent ainsi d'examiner des groupes d'animaux avec un profil de consommation homogène [43].…”