Chronic Intermittent Ethanol Exposure Produces Persistent Anxiety in Adolescent and Adult Rats

Abstract

Background Ethanol dependence and tolerance in the adult are marked by increased function of NMDA receptors and decreased function of GABAA receptors that coincides with altered receptor subunit expression in specific brain regions. Adolescents often use ethanol at levels greater than adults, yet the receptor subunit expression profiles following chronic intermittent ethanol (CIE) exposure in adolescents are not known. Persistent age-dependent changes in receptor subunit alterations coupled with withdrawal-related anxiety may help explain the increase in alcohol abuse following adolescent experimentation with the drug. Methods Adolescent and adult rats received 10 intraperitoneal administrations of 4.0 g/kg ethanol or saline every 48 hours. At either 24 hours or 12 days after the final exposure, anxiety-like behavior was assessed on the elevated plus maze and tissue was collected. Western blotting was used to assess changes in selected NMDA and GABAA receptor subunits in whole cortex and bilateral hippocampus. Results CIE exposure yields a persistent increase in anxiety-like behavior in both age groups. However, selected NMDA and GABAA receptor subunits were not differentially altered by this CIE exposure paradigm in adolescents or adults. Conclusions CIE exposure produced persistent anxiety-like behavior, which has important implications for alcohol cessation. Given the reported behavioral and neuropeptide expression changes in response to this dose of ethanol, it is important for future work to consider the circumstances under which these measures are altered by ethanol exposure.

Simvastatin treatment reduces the cholesterol content of membrane/lipid rafts, implicating the N -methyl-D-aspartate receptor in anxiety: a literature review

“…In particular, the up-regulation of different subunits of the NMDA receptor may cause hyperexcitability of the CNS during withdrawal or negative emotions such as dysphoria, irritability, anxiety, and depression (BlancoGandía et al, 2015). In accordance with numerous data in the literature, ethanol withdrawal induces an anxiogenic effect in the elevated plus-maze (Kumar et al, 2013;Van Skike, Diaz-Granados, Matthews, 2015). However, these findings contrast our previous data indicating that lower doses of ethanol produce anxiolytic-like effects (Cruz et al, 2012a).…”

Differences in Behavioral Responding in Adult and Aged Rats Following Chronic Ethanol Exposure

“…Twenty-four hours after the final EtOH exposure session, anxiety was measured using an elevated plus maze (EPM) located in a behavioral room isolated from animal housing, as previously described (Van Skike et al, 2015). Separate 1-tailed independentsamples t-tests were conducted on the percent of time spent in the open and closed arms of the maze and the number of arm entries.…”

The Detection of a GABAAR β3 Subunit in an Affinity-Purified Preparation of the GABAAR-Associated Cl-/HCO3 --ATPase Isolated from Rat Brain

“…The most common GABA A R compositions containing the β3 subunit are α3β3γ2 and α2β3γ2. The literature also shows that some GABA A R ensembles containing the β3 subunit are selectively sensitive to ethanol [32]. For example, the mammalian brain contains an ethanol-sensitive GABA A R assembly composed of α4β3δ or α6β3δ subunits [33].…”

“…To study the effect of 5mMCl -/25 mM HCO 3 -, NH 2 OH (50 mM) or EtOH (500 mM) on the phosphoprotein formation, the membrane preparation was preincubated with the ligands at 0-1° C for 20 min. Proteoliposomes with purified enzymes preparation were applied to 12 % SDS-PAGE (MOPS Denaturing Running Buffer, pH 6.0) and detected by autoradiography of 32 P. The enzyme preparations were boiled for 5 minutes in a SDS treatment buffer consisting of 50 mM MOPSTris (pH 6.0), 10 % glycerol, 5 % 2-mercaptoethanol, 2 % SDS, and 0.001 % bromophenol blue. Stained and dried gels were placed in a chamber for autoradiography (Sigma, USA) on a Hyperfilm™ MP film (Amersham, USA) and exposed at room temperature for 96 hr.…”

“…The available literature shows that direct phosphorylation of different transport P-type ATPases and Cl --ATPases can occur by [γ- 32 P]ATP in the presence of 3 mM Mg 2+ [2]. In the present work, the enzyme preparations were reconstituted into (A) The PMP (~50 μg) and PEP (~20 μg) were separated by 1-DE (hrCNE-PAGE) using a 4% to 15% gradient gel.…”