A new rat model for investigating the effects of alcohol on the adolescent brain: Acute and long-term effects

Abstract

Adolescence represents a time of unique vulnerability to improper brain maturation, due to continued development of some frontal regions of the brain and a propensity for risky behaviours including alcohol use. Recently, in New Zealand and overseas, increases in binge drinking during adolescence have necessitated further research into alcohol’s short- and long-term effects on the brain and behaviour. Important research using animal models has revealed gross changes in brain structure and function in response to large alcohol doses, however it is still not known what subtle changes, if any, may result from binge drinking at the levels that are seen in the majority of the population. The current study aims to address this by using Long-Evans rats to model moderate- to high-levels of weekly binge drinking in human adolescents. Male and female rats were given 9.0 g/kg/day alcohol by intra-gastric gavage, every fourth day from PN28 to 48, resulting in a mean peak BEC on alcohol dosing days of 277 mg/dL. Control animals were not given alcohol. The brains of the rats were investigated immediately following alcohol treatment (ages PN29, PN33, PN37, PN41, PN45 and PN49) for presence of apoptotic cell death and gliosis. A battery of behavioural tests was completed up to a year of post-natal age in order to investigate changes in brain function that persist in the long-term Histological survey throughout the cerebrum revealed no apoptosis, which could be consistent with an insult, after any of the 6 alcohol treatments. There were, however, subtle differences in astrocyte number in the rostral cingulate cortex, which require further study. Behavioural tests revealed subtle differences in performance between treatment/sex groups in key areas, despite a considerable period of abstinence. Of particular interest was an alcohol-induced reduction in working memory performance, during recognition of a novel object, that affected male but not female rats. Male, alcohol-treated rats also were less accurate at finding the platform in the initial stages of the MWM probe trial, as evidenced by fewer crossings of the previous platform location. This finding was not replicated in the female rats. Female rats that had been treated with alcohol during adolescence did, however, spent a significantly greater percentage of their path length in the outer zone of the MWM during the probe trial and this behaviour is normally indicative of a non-problem solving, panic response.