Social and anxiety-like behaviors contribute to nicotine self-administration in adolescent outbred rats

Abstract

Both emotional and social traits interact with genetic factors to influence smoking behavior. We previously established a socially acquired nicotine intravenous self-administration model where social learning of a nicotine-associated odor cue reversed conditioned flavor aversion and promoted nicotine intake. In this study, we first phenotyped ~800 adolescent heterogeneous stock rats in open field, novel object interaction, social interaction, elevated plus maze, and marble burying behaviors. These rats were then phenotyped on socially acquired nicotine self-administration. We found 243 significant correlations between different behavioral tests. Principal component regression analysis found that ~10–20% of the variance in nicotine-related measures, such as intake during the first or the last three fixed-ratio sessions, the progressive ratio session, and reinstatement behavior, can be explained by variations in behavioral traits. Factors corresponding to social behavior and anxiety were among the strongest predictors of nicotine intake and reinstatement of nicotine-seeking behavior. We also found many sex differences in behavioral measures. These data indicated that the genetic diversity of this population, in combination with social behaviour and anxiety, are significant contributors to the divergent nicotine self-administration behavior and indicated a high probability of discovering sex-specific genetic mechanisms for nicotine intake in future genome-wide association studies.

Genome-wide association study of open field behavior in outbred heterogeneous stock rats identifies multiple loci implicated in psychiatric disorders

“…With over 1,200 rats, ours represent some of the largest data collected using these assays. Similar to our interim report on this data set [27], we found a large number of correlations with relatively low coefficients (e.g., r < 0.4) but with high statistical significance. It is likely that these correlated traits are controlled by the same behavioral processes and thus are influenced by the same genetic factors.…”

“…As part of a GWAS on intravenous nicotine self-administration in adolescent HS rats that we are conducting [27,37], we collected several behavioral phenotypes related to anxiety, novelty exploration, and social interaction. We have previously reported that these behavioral traits contribute to the variation in nicotine intake [27]. We report here GWAS results of three behavioral traits: OFT, NOIT, and SIT, which were all conducted in the same open field.…”

“…Here we report the results on associations of genomic loci with measures obtained from OFT, NOIT and SIT. These analyses were based on an expanded data set that contained about twice the sample size of that reported previously [27]. These data were collected as part of a larger GWAS on socially acquired nicotine intravenous self-administration, which will be the subject of a separate publication.…”

Establishment of Multi-stage Intravenous Self-administration Paradigms in Mice

“…Extracted components and drug-induced locomotion data were treated as features to build multiple linear regressions using the 'lm' function in R-Studio. The 'step' function was used to select independent variables based on Akaike information criterion (63,64). The trained models were applied to test datasets to make predictions.…”

Interaction Between Smoking and Internet Gaming Disorder on Spontaneous Brain Activity

“…Smoking group demonstrated significantly higher SAS, SDS, and impulsivity scores, which is consistent with previous studies that smoking was associated with anxiety and depression with smoking ( 34 ). Anxiety was one of the strongest predictors of nicotine intake and nicotine-seeking behavior ( 35 ) and significantly related to the severity of cigarette dependence and unsuccessful attempts to quit ( 36 ). Similar reports have been made of depression that compared with persons without depression, depressed individuals are more likely to smoke and relapse, less likely to quit ( 37 ).…”