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

Tengfei Wang,Apurva S. Chitre,Leah C. Solberg Woods,Hao Chen,Oksana Polesskaya,Abraham A. Palmer,Wenyan Han

doi:10.1038/s41598-018-36263-w

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.

Highlights

Smoking behavior is affected by a myriad of environmental and genetic factors
Two male and two female rats per litter were used for behavioral studies
Each of the ~800 adolescent heterogeneous stock rats was first tested on five behavioral tests, including Open field test (OFT), Novel object interaction test (NOIT), Social interaction test (SIT), Elevated plus maze test (EPM), and Marble bury test (MBT)

Summary

Introduction

Smoking behavior is affected by a myriad of environmental and genetic factors. The strong influence of social environment in smoking initiation, especially during adolescence, the most critical age for smoking initiation[1], is well-documented[2,3]. We have developed a rat model of adolescent nicotine intravenous self-administration (IVSA) that captures the role of social learning in promoting nicotine intake. This operant licking model delivers intravenous nicotine with a contingent flavor (i.e., taste and odor) cue. One fundamental finding from this model was that rats trained alone in a operant chamber developed conditioned flavor aversion and failed to self-administer nicotine. Interacting with another rat that consumed the same flavor cue during training reversed the conditioned aversive response and promoted nicotine intake[17]. The taste cue did not appear to be important[17]

Methods

Results

Conclusion