Effect of sub-chronic intermittent ethanol exposure on spatial learning and ethanol sensitivity in adolescent and adult rats

Abstract

It has become clear that adolescence is a period of distinct responsiveness to the acute effects of ethanol on learning and other cognitive functions. However, the effects of repeated intermittent ethanol exposure during adolescence on learning and cognition are less well studied, and other effects of repeated ethanol exposure such as withdrawal and chronic tolerance complicate such experiments. Moreover, few studies have compared the effects of repeated ethanol exposure during adolescence and adulthood, and they have yielded mixed outcomes that may be related to methodological differences and/or secondary effects of ethanol on behavioral performance. One emerging question is whether relatively brief intermittent ethanol exposure (i.e., sub-chronic exposure) during adolescence or adulthood might alter learning at a time after exposure when chronic tolerance would be expected, and whether tolerance to the cognitive effects of ethanol might influence the effect of ethanol on learning at that time. To address this, male adolescent and adult rats were pre-treated with sub-chronic daily ethanol (five doses [4.0 g/kg, i.p.] or saline at 24-h intervals, across 5 days). Two days after the last pre-exposure, spatial learning was assessed on 4 consecutive days using the Morris water maze. Half of the animals from each treatment cell received ethanol (2.0 g/kg, i.p.) 30 min prior to each testing session and half of the animals received saline. Ethanol pre-exposure altered water maze performance in adolescent animals but not in adults, and acute ethanol exposure impaired learning in animals of both ages independent of pre-exposure condition. There was no evidence of cognitive tolerance in animals of either age group. These results indicate that a relatively short period of intermittent ethanol exposure during adolescence, but not adulthood, alters baseline water maze performance shortly after pre-exposure and does not induce cognitive tolerance to the effects of ethanol in either age group.

Adolescent binge ethanol exposure alters specific forebrain cholinergic cell populations and leads to selective functional deficits in the prefrontal cortex

“…Similar to the findings presented here, we previously found that intermittent ethanol exposure during early and mid adolescence, as well as adulthood, did not affect spatial memory assessed by performance on a spontaneous alternation task (Fernandez et al, 2017). Additionally, AIE does not yield acquisition impairments on the Morris water maze, radial arm maze or the Barnes maze (Van Skike et al, 2012; Risher et al, 2013; Swartzwelder et al, 2014). In the current study, we also found spatial learning to be unaffected by AIE when assessed using a Barnes maze.…”

Chronic intermittent ethanol exposure leads to alterations in brain-derived neurotrophic factor within the frontal cortex and impaired behavioral flexibility in both adolescent and adult rats

“…Spatial memory is also unaffected following either adolescent or adult CIE in a radial arm maze task, but an acute EtOH challenge did alter path efficiency in both age groups (Swartzwelder et al, 2014). Our findings add to the growing evidence that chronic, binge-like levels of EtOH during adolescence or adulthood does not negatively affect spatial memory when tested in a drug-free state.…”

Neuroimmune Basis of Alcoholic Brain Damage

“…Multiple studies on adults following adolescent behavior done by NADIA investigators Linda Spear and Scott Swartzwelder find an altered adult that has persistent adolescent-like responses in adulthood. Studies of spatial learning in the radial arm maze find adolescence, but not adult, ethanol treatment models result in high adolescent-like sensitivity to ethanol memory impairment persisting into adulthood (Swartzwelder et al, 2014; White, Ghia, Levin, & Swartzwelder, 2000). Similarly, adolescent ethanol binge models produce a long-lasting decrease in sensitivity to the sedative/motor-impairing effects of acute ethanol, i.e., an adolescent-like low response persisting into adulthood (White, Truesdale, et al, 2002).…”