A characteristic of alcoholism is an increased incentive motivation for ethanol. Incentive motivation is comprised of the motivation to respond for ethanol and the hedonic value of ethanol. Early drinking onset is correlated with an earlier onset of alcoholism, a stronger severity of alcohol dependence, and increased deficits in neuronal microstructure. While drinking rates in males and females are relatively similar during adolescence, exposure to ethanol during adolescence results in more damage to the neuronal microstructure in females while more males develop alcohol-use disorders in adulthood. In rodents, differential rearing environments during childhood and adolescence result in plasticity- dependent neuronal changes. These neuronal changes impact a variety of behaviors, including the response to ethanol. Rearing rats in an enriched condition decreases responding for ethanol in operant ethanol self-administration when compared to rats raised in an isolated or standard condition. The overarching goal of the proposed experiments is to determine if differential rearing-induced plasticity alters the integrity of the neuronal microstructure to affect both the hedonic value and the incentive salience for ethanol in adulthood. It is hypothesized that rearing male and female rats in an enriched environment will decrease hedonic responses to ethanol when compared to rearing male and female rats in an isolated or standard environment. The proposed experiments will also determine if differential rearing during intermittent adolescent ethanol exposure can alter the hedonic value and incentive salience for ethanol in adulthood. It is predicted that enrichment during adolescent ethanol exposure will protect against the increased risk for alcoholism in adulthood in both male and female rats. The proposed experiments will then examine how differential rearing during adolescent ethanol exposure alters the neuronal microstructure using diffusion tension imaging. It is predicted that rearing in an enriched environment will protect against the deleterious effects of ethanol exposure in adolescence when compared to rats reared in an isolated or social condition. We further predict that sex will alter the effects of adolescent ethanol exposure on neuronal microstructure integrity and therefore female isolated rats will have the most damage to the neuronal microstructure as a result of adolescent ethanol exposure. Completion of the project will determine that differential rearing alters incentive motivation for ethanol due to alterations of neuronal microstructure integrity. Development of this model will provide us the ability to test behavioral and neurobiological changes that result from adolescent ethanol exposure in a preclinical model system that results in divergent outcomes for both plasticity and ethanol sensitivity.
Rearing in an enriched environment during adolescence protects against alcohol use while rearing in an isolated environment increases susceptibility to alcohol use. This proposal will explore if differential rearing-induced alterations in neuronal microstructure contribute to the differences in alcohol use vulnerability in adulthood. The findings of this research are intended to advance the understanding of the basic neural mechanisms mediating the effects of the environment on alcohol use and abuse.
| Wukitsch, Thomas Joseph; Reinhardt, Emily Kae; Kiefer, Stephen W et al. (2018) Voluntary ethanol consumption during early social isolation and responding for ethanol in adulthood. Alcohol : |
| Pajser, Alisa; Breen, Morgan; Fisher, Hayley et al. (2018) Individual differences in conditioned fear are associated with levels of adolescent/early adult alcohol consumption and instrumental extinction. Behav Brain Res 349:145-157 |
