Adolescent intermittent alcohol exposure produces strain-specific cross-sensitization to nicotine and other behavioral adaptations in adulthood in C57BL/6J and DBA/2J mice

Laurel R Seemiller; Prescilla Garcia-Trevizo; Carlos Novoa; Lisa R Goldberg; Samantha Murray; Thomas J Gould

doi:10.1016/j.pbb.2023.173655

Adolescent intermittent alcohol exposure produces strain-specific cross-sensitization to nicotine and other behavioral adaptations in adulthood in C57BL/6J and DBA/2J mice

Pharmacol Biochem Behav. 2023 Oct 5:232:173655. doi: 10.1016/j.pbb.2023.173655. Online ahead of print.

Authors

Laurel R Seemiller¹, Prescilla Garcia-Trevizo¹, Carlos Novoa¹, Lisa R Goldberg¹, Samantha Murray¹, Thomas J Gould²

Affiliations

¹ Department of Biobehavioral Health, Penn State University, University Park, PA, USA.
² Department of Biobehavioral Health, Penn State University, University Park, PA, USA. Electronic address: tug70@psu.edu.

PMID: 37802393
PMCID: PMC10995114 (available on 2025-04-05)
DOI: 10.1016/j.pbb.2023.173655

Abstract

Adolescent alcohol exposure is associated with lasting behavioral changes in humans and in mice. Prior work from our laboratory and others have demonstrated that C57BL/6J and DBA/2J mice differ in sensitivity to some effects of acute alcohol exposure during adolescence and adulthood. However, it is unknown if these strains differ in cognitive, anxiety-related, and addiction-related long-term consequences of adolescent intermittent alcohol exposure. This study examined the impact of a previously validated adolescent alcohol exposure paradigm (2-3 g/kg, i.p., every other day PND 30-44) in C57BL/6J and DBA/2J male and female mice on adult fear conditioning, anxiety-related behavior (elevated plus maze), and addiction-related phenotypes including nicotine sensitivity (hypothermia and locomotor depression) and alcohol sensitivity (loss of righting reflex; LORR). Both shared and strain-specific long-term consequences of adolescent alcohol exposure were found. Most notably, we found a strain-specific alcohol-induced increase in sensitivity to nicotine's hypothermic effects during adulthood in the DBA/2J strain but not in the C57BL/6J strain. Conversely, both strains demonstrated a robust increased latency to LORR during adulthood after adolescent alcohol exposure. Thus, we observed strain-dependent cross-sensitization to nicotine and strain-independent tolerance to alcohol due to adolescent alcohol exposure. Several strain and sex differences independent of adolescent alcohol treatment were also observed. These include increased sensitivity to nicotine-induced hypothermia in the C57BL/6J strain relative to the DBA/2J strain, in addition to DBA/2J mice showing more anxiety-like behaviors in the elevated plus maze relative to the C57BL/6J strain. Overall, these results suggest that adolescent alcohol exposure results in altered adult sensitivity to nicotine and alcohol with some phenotypes mediated by genetic background.

Keywords: Adolescent; Alcohol; Anxiety; Behavior; Drug sensitivity; Fear conditioning; Hypothermia; Intermittent; LORR; Learning; Locomotor; Nicotine; Righting reflex.

Abstract

Grants and funding