Impact of Adolescent Intermittent Ethanol on Noradrenergic Development

Abstract

In clinical populations, adolescent alcohol drinking has been shown to increase stress sensitivity and the likelihood of developing alcohol use disorders (AUDs) in adulthood. These findings suggest pathways mediating stress‐relating behaviors are impacted by developmental exposure to alcohol, contributing to a greater risk for alcoholism and potentially stress‐induced relapse following treatment. Animal models indicate tyrosine hydroxylase (TH) neurons in the A2 region of the nucleus of the tractus solitarius (NTS) contribute to stress‐induced relapse through enhanced norepinephrine signaling, subsequently increasing neuronal activity in the bed nucleus of the stria terminalus (BNST). Previous research suggests NTS TH expression undergoes developmental changes during adolescence that may make this neuronal population susceptible to modulation by alcohol during this age. We hypothesized adolescent intermittent ethanol (AIE) exposure in mice, a standard preclinical model of adolescent binge drinking, will impact NTS TH neuron development, ultimately altering the NTS‐BNST circuitry resulting in a higher risk of AUDs in adulthood. NTS TH mRNA expression in male and female C57Bl6/J mice exposed to AIE (postnatal day [PND] 28–42) or used as air controls was quantified via qRT‐PCR at different time points (PND29, PND36, PND43, PND49, PND70). Immunohistochemistry methods were implemented to determine the impact of AIE on NTS TH neuronal activity following an ethanol challenge in adulthood (PND70). Results showed a significant increase in TH mRNA in males one day after beginning AIE (PND29) relative to air controls, while females exhibited the greatest TH expression after their first week of exposure to ethanol (PND36). In both sexes, heightened TH mRNA expression occurred earlier than expected during normal development. Surprisingly, compared to adult ethanol naïve mice, AIE decreased the ability of ethanol at doses of 2g/kg and 4g/kg to alter NTS TH neuron cFos expression at PND70 compared to control. Together, these findings suggest an enhancement of NTS TH activity early in development and reduction of ethanol sensitivity in adulthood. Studies are in progress to further delineate the mechanisms by which AIE reduces adult ethanol sensitivity and how this may alter stress‐related behaviors.Support or Funding InformationAA22937AA017823This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.