Adolescent alcohol-drinking leads to long lasting changes in the medial prefrontal cortex

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Simpson, Zakery; Hernandez, Liza J.; Deehan, Gerald A., 2024384
Biological Psychology
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A significant number of individuals begin drinking alcohol early in life during adolescence, a period in which their brain is developing. Drinking alcohol at an early age is linked to a greater likelihood that a person will become an alcoholic later in life. Levels of Glutamate (GLU), a major neurotransmitter, in the medial prefrontal cortex (mPFC) has been directly linked to the expression of alcohol-use disorders. Thus, a better understanding of how childhood drinking produces alterations in the brain, thereby contributing to alcoholism, is needed. The current research utilized an animal model of alcoholism to examine the long range consequences of alcohol consumption during adolescence on GLU functioning within the mPFC in adulthood. It was hypothesized, adolescent drinking would lead to a higher levels of GLU in the mPFC in adulthood. Two groups of alcohol-preferring (P) rats received either free-access to alcohol (15% v/v) and water or water alone in their home cage (24 hrs a day; 7 days a week) during their adolescent period. At the end of the adolescent period, alcohol was removed and all animals were provided only water to drink for approximately 21 days. Next, animals were implanted with guide cannula aimed at infralimbic and prelimbic regions of the mPFC and provided one-week to recover before undergoing quantitative microdialysis, a method that allows for the direct sampling of GLU from brain tissue. During testing, samples were collected every 10 minutes and animals were first exposed to artificial cerebral spinal fluid (aCSF) followed by aCSF containing three GLU concentrations (1 µM, 5 µM , and 10 µM; presented in randomized order across rats). By exposing the animals to different levels of GLU, the average brain level of GLU can be established as well as how fast the brain is removing/clearing GLU. Samples were analyzed using high-pressure liquid chromatography a method that quantifies GLU levels in each sample. Analyses revealed a significantly lower level of GLU removal/clearance in the prelimbic region of the mPFC of the alcohol-drinking group compared to the water group. Analyses also revealed a significantly higher average level of GLU in the alcohol-drinking group compared to the water drinking control group. There were no differences between groups in average GLU levels or GLU clearance in the infralimbic region of the mPFC. Overall, the data from the current study suggest that the consumption of alcohol during adolescence may produce a long-lasting reduction of GLU removal/clearance thereby resulting in increased GLU levels within the prelimbic region of the mPFC. The current findings may represent a long-lasting change that happens in the brain when an individual consumes alcohol during adolescence which could then contribute to the development of an alcohol-use disorder later in life.