Voluntary Ethanol Consumption and Alterations in Reward Circuitry in Ethanol Exposed Adolescent Male Mice

Publication Date

July 2019

Location

LSU Health Medical Education Building

Document Type

Abstract

Start Date

26-7-2019 9:00 AM

End Date

26-7-2019 12:00 PM

Description

Adolescent drinking has been shown to contribute to the development of alcohol use disorders (AUDs) later in life. Our lab utilizes a mouse model of adolescent intermittent alcohol vapor exposure (AIE) to study neuroadaptations and behavioral correlates of this early alcohol use. One brain region of particular interest is the bed nucleus of the stria terminalis (BNST), which is a key brain structure in mediating both reward and stress/negative affect related behaviors. Thus, it is critical to understand how adolescent alcohol affects the BNST. Previous work in the lab has demonstrated that withdrawal from AIE enhances glutamate release and subsequent excitatory plasticity in the BNST, yet the specific inputs and cell populations affected are still unknown. The current work set out to test two hypotheses: 1) withdrawal from AIE increases the activity of BNST inputs from areas involved in reward and 2) AIE enhances subsequent voluntary alcohol intake. To test this, male C57BL/6J mice underwent adolescent intermittent ethanol vapor exposure (AIE) consisting of two four-day cycles (16hrs in, 8hrs out) separated by three non-vapor chamber days. One cohort first received bilateral microinjections of fluorescent green retrobead tracer into the BNST and then underwent AIE treatment. Green retrobeads are used to identify those brain regions that send projections to the BNST. These mice were perfused during withdrawal from AIE (4-6hrs after final vapor exposure), had their brains removed and were subsequently processed using immunohistochemistry for the immediate early gene, c-fos. This strategy allows us to determine if acute withdrawal alters the activation from reward brain structures projecting to the BNST (nucleus accumbens shell, ventral tegmental area, prefrontal cortex, peri-aquiductal gray, and hippocampus). A second group of mice received a two-bottle choice (2BC) voluntary alcohol consumption protocol following AIE. In 2BC, subjects were allowed intermittent, 24hr access to 20% alcohol solution or water, separated by 24 hr withdrawal periods, where they were provided only water. Voluntary ethanol consumption in 2BC was monitored for four-weeks following AIE or air vapor exposure. There was no significant interaction between history of vapor treatment and alcohol consumption or alcohol preference (p’s>.05). However, a main effect of time was significant for alcohol consumption, alcohol preference, and water consumption (p’s<.002). These results do not replicate previous findings that alcohol vapor exposure increases voluntary alcohol consumption in rats and suggest potential differences across rodent models. Future work will continue to quantify changes in reward circuitry inputs into the BNST from adolescent alcohol exposure.

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Mentor: Tiffany Wills, Department of Cell Biology & Anatomy

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Jul 26th, 9:00 AM Jul 26th, 12:00 PM

Voluntary Ethanol Consumption and Alterations in Reward Circuitry in Ethanol Exposed Adolescent Male Mice

LSU Health Medical Education Building

Adolescent drinking has been shown to contribute to the development of alcohol use disorders (AUDs) later in life. Our lab utilizes a mouse model of adolescent intermittent alcohol vapor exposure (AIE) to study neuroadaptations and behavioral correlates of this early alcohol use. One brain region of particular interest is the bed nucleus of the stria terminalis (BNST), which is a key brain structure in mediating both reward and stress/negative affect related behaviors. Thus, it is critical to understand how adolescent alcohol affects the BNST. Previous work in the lab has demonstrated that withdrawal from AIE enhances glutamate release and subsequent excitatory plasticity in the BNST, yet the specific inputs and cell populations affected are still unknown. The current work set out to test two hypotheses: 1) withdrawal from AIE increases the activity of BNST inputs from areas involved in reward and 2) AIE enhances subsequent voluntary alcohol intake. To test this, male C57BL/6J mice underwent adolescent intermittent ethanol vapor exposure (AIE) consisting of two four-day cycles (16hrs in, 8hrs out) separated by three non-vapor chamber days. One cohort first received bilateral microinjections of fluorescent green retrobead tracer into the BNST and then underwent AIE treatment. Green retrobeads are used to identify those brain regions that send projections to the BNST. These mice were perfused during withdrawal from AIE (4-6hrs after final vapor exposure), had their brains removed and were subsequently processed using immunohistochemistry for the immediate early gene, c-fos. This strategy allows us to determine if acute withdrawal alters the activation from reward brain structures projecting to the BNST (nucleus accumbens shell, ventral tegmental area, prefrontal cortex, peri-aquiductal gray, and hippocampus). A second group of mice received a two-bottle choice (2BC) voluntary alcohol consumption protocol following AIE. In 2BC, subjects were allowed intermittent, 24hr access to 20% alcohol solution or water, separated by 24 hr withdrawal periods, where they were provided only water. Voluntary ethanol consumption in 2BC was monitored for four-weeks following AIE or air vapor exposure. There was no significant interaction between history of vapor treatment and alcohol consumption or alcohol preference (p’s>.05). However, a main effect of time was significant for alcohol consumption, alcohol preference, and water consumption (p’s<.002). These results do not replicate previous findings that alcohol vapor exposure increases voluntary alcohol consumption in rats and suggest potential differences across rodent models. Future work will continue to quantify changes in reward circuitry inputs into the BNST from adolescent alcohol exposure.