Behavioral Profiles of Adolescent Alcohol-Preferring/Non-preferring (P/NP) and High/Low Alcohol-Drinking (HAD/LAD) Rats Are Dependent on Line but Not Sex.

Stina Lundberg,Erika Roman,Richard L Bell

doi:10.3389/fnins.2021.811401

Abstract

Initial contact with alcohol generally occurs during adolescence, and high consumption during this period is associated with increased risk for later alcohol (AUDs) and/or substance use disorders (SUDs). Rodents selectively bred for high or low alcohol consumption are used to identify behavioral characteristics associated with a propensity for high or low voluntary alcohol intake. The multivariate concentric square field™ (MCSF) is a behavioral test developed to study rodents in a semi-naturalistic setting. Testing in the MCSF creates a comprehensive behavioral profile in a single trial. The current aim was to examine the behavioral profiles of adolescent, bidirectionally selectively bred male and female high alcohol-consuming (P and HAD1/2) and low alcohol-consuming (NP and LAD1/2) rat lines, and outbred Wistar rats. Alcohol-naïve rats were tested once in the MCSF at an age between postnatal days 30 and 35. No common behavioral profile was found for either high or low alcohol-consuming rat lines, and the effect of sex was small. The P/NP and HAD2/LAD2 lines showed within pair-dependent differences, while the HAD1/LAD1 lines were highly similar. The P rats displayed high activity and risk-associated behaviors, whereas HAD2 rats displayed low activity, high shelter-seeking behavior, and open area avoidance. The results from P rats parallel clinical findings that denser family history and risk-taking behavior are strong predictors of future AUDs, often with early onset. Contrarily, the HAD2 behavioral profile was similar to individuals experiencing negative emotionality, which also is associated with a vulnerability to develop, often with a later onset, AUDs and/or SUDs.

Highlights

Addiction is a complex disorder that is influenced by environmental factors and their interaction with a genetic make-up
Females weighed less than males in P, NP, and Wistar animals, while no sex-dependent differences were detected in HAD1, LAD1, HAD2, or LAD2 rats
A corollary is that differences found within any individual line-pair does not necessarily represent all phenotypic differences observed between individuals who are family history positive (FHP) or negative (FHN) for alcohol use disorders (AUDs)

Summary

Introduction

Addiction is a complex disorder that is influenced by environmental factors and their interaction with a genetic make-up. To examine the heritability of a vulnerability to develop AUDs, bidirectional selective breeding strategies in laboratory animals have been used (Bell et al, 2012, 2016, 2017). Bred lines have made it possible to determine behavioral (Roman et al, 2012), neurobiological (Bell et al, 2012), and genetic (McBride et al, 2012; Bell et al, 2017) characteristics associated with selection for high vs low voluntary alcohol consumption. Little is known about alcohol-naïve adolescent behavior of these lines, especially in females, and such studies would provide further information regarding modeling of family history for AUDs during development (Bell et al, 2013, 2014)

Objectives

Methods

Results

Discussion

Conclusion