Impact of adolescent intermittent ethanol exposure in male and female rats on social drinking and neuropeptide gene expression

Abstract

Background Alcohol use during adolescence can alter maturational changes that occur in brain regions associated with social and emotional responding. Our previous studies have shown that adult male, but not female rats demonstrate social anxiety‐like alterations and enhanced sensitivity to ethanol‐induced social facilitation following adolescent intermittent ethanol exposure (AIE). These consequences of AIE may influence adult social drinking in a sex‐specific manner. Methods To test the effects of AIE on social drinking, male and female Sprague‐Dawley rats exposed to water or ethanol (0 or 4 g/kg, intragastrically, every other day, between postnatal day [P] 25 and 45) were tested as adults (P72‐83) in a social drinking paradigm (30‐minute access to a 10% ethanol solution in supersac or supersac alone in groups of three same‐sex littermates across two 4‐day cycles separated by 4 days off). Social behavior was assessed during the last drinking session, along with assessment of oxytocin (OXT), oxytocin receptor (OXTR), vasopressin (AVP), and vasopressin receptors 1a and 1b (AVPR1a, AVPR1b) in the hypothalamus and lateral septum. Results Males exposed to AIE consumed more ethanol than water‐exposed controls during the second drinking cycle, whereas AIE did not affect supersac intake in males. AIE‐exposed females consumed less ethanol and more supersac than water‐exposed controls. Water‐exposed females drinking ethanol showed more social investigation and significantly higher hypothalamic OXTR, AVP, and AVPR1b gene expression than their counterparts ingesting supersac and AIE females drinking ethanol. In males, hypothalamic AVPR1b gene expression was affected by drinking solution, with significantly higher expression evident in males drinking ethanol than those consuming supersac. Conclusions Collectively, these findings provide new evidence regarding sex‐specific effects of AIE on social drinking and suggest that the hypothalamic OXT and AVP systems are implicated in the effects of ingested ethanol on social behavior in a sex‐ and adolescent‐exposure‐dependent manner.

Determining the neuronal ensembles underlying sex-specific social impairments following adolescent intermittent ethanol exposure

“…Specifically, males exposed to ethanol during adolescence show decreased social preference and social investigation, with these findings absent in females. Furthermore, these male specific social deficits may increase the propensity for AIE-exposed males to consume ethanol when in a social environment (Towner et al, 2022b). However, our understanding of the neural mechanisms regulating AIE-induced social deficits are still limited.…”

Binge eating promotes ethanol self-administration in female rats with a history of intermittent ethanol exposure at adolescence

“…termination of the IEA protocol. More recently researchers (Towner et al, 2022) gave male and female Wistar rats 4 g/kg ethanol, i.g., every other day on PD25-45 and then tested the rats at PD72-83 for intake of 10% ethanol under social circumstances. This procedure yielded significantly less ethanol intake in IEA vs. control females and either no effect or a mild and transient promoting effect upon ethanol intake in the males.…”

Prelimbic cortex perineuronal net expression and social behavior: Impact of adolescent intermittent ethanol exposure

“…Tissue micropunches containing the mPFC (PrL and Infralimbic (IL)) were taken and processed using protocols previously described (Towner et al, 2022b). In short, we used a phenol-chloroform extraction with Qiagen RNAeasy kits (Qiagen, Hilden, Germany) according to the manufacturer instructions.…”