Social learning promotes nicotine self-administration by facilitating the extinction of conditioned aversion in isogenic strains of rats

Wenyan Han,Tengfei Wang,Hao Chen

doi:10.1038/s41598-017-08291-5

Wenyan Han, Tengfei Wang + Show 1 more

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https://doi.org/10.1038/s41598-017-08291-5

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Abstract

Both social environment and genetic factors are critical for smoking initiation and nicotine addiction. We reported that rats developed conditioned flavor (i.e., taste and odor) aversion to intravenously self-administered (IVSA) nicotine, and that social learning promoted nicotine IVSA with flavor cues. We thus tested the hypothesis that socially acquired nicotine IVSA is a heritable trait by using female rats of six inbred strains and six F1 hybrids. Each strain was tested for 10 daily IVSA sessions. We found that the intake of nicotine (15 and 30 μg/kg/inf) varied among these strains by 33.7–56.6-fold. The heritability of nicotine intake was estimated to be 0.54–0.65. Further, there was a strong correlation in nicotine intake (R2 = 0.85, p < 0.0001) between the two nicotine doses. Another cohort of rats was given three daily IVSA sessions followed by five sessions that tested conditioned flavor aversion. Nicotine intake was highly correlated with the extinction of the conditioned aversion (R2 = 0.58, p < 0.005). These data showed that nicotine intake in the socially acquired nicotine self-administration model is controlled by genetic factors and that the role of social learning is likely in facilitating the extinction of conditioned aversive response to nicotine.

Highlights

Nicotine is the principal psychoactive ingredient of tobacco products1
Many studies have confirmed that variations in the CHRNA3-CHRNA5-CHRNB4 gene cluster are associated with smoking, the number of cigarettes consumed per day12
We previously reported that genetic factors contributed to nicotine intravenous self-administration (IVSA) and food reward by using a lever press model in isogenic strains of adolescent rats16

Summary

Introduction

Nicotine is the principal psychoactive ingredient of tobacco products. It exerts marked reinforcing effects and maintains drug-seeking behavior . The aversive nature of nicotine indicates that smoking initiation is likely influenced by other factors that could reduce the negative motivational effect of nicotine. One example of such a factor is the social environment. Many studies have confirmed that variations in the CHRNA3-CHRNA5-CHRNB4 gene cluster are associated with smoking, the number of cigarettes consumed per day12 Genes in this cluster, especially CHRNA5, have been shown to underlie the aversive effect of nicotine . We previously reported that genetic factors contributed to nicotine IVSA and food reward by using a lever press model in isogenic strains of adolescent rats Correspondence and requests for materials should be addressed to H.C. (email: hchen@uthsc. edu) www.nature.com/scientificreports/

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