Abstract
BackgroundAdolescence is not only a critical period of late-stage neurological development in humans, but is also a period in which ethanol consumption is often at its highest. Given the prevalence of ethanol use during this vulnerable developmental period we assessed the long-term effects of chronic intermittent ethanol (CIE) exposure during adolescence, compared to adulthood, on performance in the radial-arm maze (RAM) and operant food-reinforced responding in male rats.Methodology/Principal FindingsMale Sprague Dawley rats were exposed to CIE (or saline) and then allowed to recover. Animals were then trained in either the RAM task or an operant task using fixed- and progressive- ratio schedules. After baseline testing was completed all animals received an acute ethanol challenge while blood ethanol levels (BECs) were monitored in a subset of animals. CIE exposure during adolescence, but not adulthood decreased the amount of time that animals spent in the open portions of the RAM arms (reminiscent of deficits in risk-reward integration) and rendered animals more susceptible to the acute effects of an ethanol challenge on working memory tasks. The operant food reinforced task showed that these effects were not due to altered food motivation or to differential sensitivity to the nonspecific performance-disrupting effects of ethanol. However, CIE pre-treated animals had lower BEC levels than controls during the acute ethanol challenges indicating persistent pharmacokinetic tolerance to ethanol after the CIE treatment. There was little evidence of enduring effects of CIE alone on traditional measures of spatial and working memory.Conclusions/SignificanceThese effects indicate that adolescence is a time of selective vulnerability to the long-term effects of repeated ethanol exposure on neurobehavioral function and acute ethanol sensitivity. The positive and negative findings reported here help to further define the nature and extent of the impairments observed after adolescent CIE and provide direction for future research.
Highlights
Adolescence is a critical period for synaptic pruning and refinement across neocortical and non-neocortical regions
All animals were exposed to a chronic intermittent ethanol (CIE) exposure regimen consisting of 10 doses of 5 g/kg ethanol (35% v/ v in saline at 18.12 mL/kg) or isovolumetric saline administered by intragastric gavage (IG) using a 2 days on, 2 days off intermittent schedule for 20 days followed by a 20 day washout period, allowing all animal to reach adulthood prior to behavioral testing
We found that CIE exposure during adolescence altered radial-arm maze (RAM) performance during an acute EtOH challenge in adulthood, whereas CIE during adulthood did not
Summary
Adolescence is a critical period for synaptic pruning and refinement across neocortical and non-neocortical regions (e.g., hippocampus) This process occurs throughout adolescence and continues into young adulthood [1,2,3,4]. Prolonged maturation in areas required for complex cognitive processes may be responsible for the limited planning, foresight and impulse control commonly observed among adolescents [5]. Ethanol (EtOH) consumption is often initiated and occurs at its highest levels during adolescence and young adulthood [7] These phenomena can coalesce, resulting in an escalation of risky behavior and the onset of alcohol use disorders (AUD) [8,9,10], which can adversely affect an individual’s development into adulthood. Given the prevalence of ethanol use during this vulnerable developmental period we assessed the long-term effects of chronic intermittent ethanol (CIE) exposure during adolescence, compared to adulthood, on performance in the radial-arm maze (RAM) and operant food-reinforced responding in male rats
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