Immediate early gene expression reveals interactions between social and nicotine rewards on brain activity in adolescent male rats

Abstract

Smoking initiation predominantly occurs during adolescence, often in the presence of peers. Therefore, understanding the neural mechanisms underlying the rewarding effects of nicotine and social stimuli is vital. Using the conditioned place preference (CPP) procedure, we measured immediate early gene (IEG) expression in animals following exposure either to a reward-conditioned environment or to the unconditioned stimuli (US). Adolescent, male rats were assigned to the following CPP US conditions: (1) Saline + Isolated, (2) Nicotine + Isolated, (3) Saline + Social, or (4) Nicotine + Social. For Experiment 1, brain tissue was collected 90 min following the CPP expression test and processed for Fos immunohistochemistry. We found that rats conditioned with nicotine with or without a social partner exhibited CPP; however, we found no group differences in Fos expression in any brain region analyzed, with the exception of the nucleus accumbens core that exhibited a social-induced attenuation in Fos expression. For Experiment 2, brain tissue was collected 90 min following US exposure during the last conditioning session. We found social reward-induced increases in IEG expression in striatal and amydalar subregions. In contrast, nicotine reduced IEG expression in prefrontal and striatal subregions. Reward interactions were also found in the dorsolateral striatum, basolateral amygdala, and ventral tegmental area where nicotine alone attenuated IEG expression and social reward reversed this effect. These results suggest that in general social rewards enhance, whereas nicotine attenuates, activation of mesocorticolimbic regions; however, the rewards given together interact to enhance activation in some regions. The findings contribute to knowledge of how a social environment influences nicotine effects.

Social context has differential effects on acquisition of nicotine self-administration in male and female rats

“…Consistent with this idea, we have shown that nicotine and social reward interact synergistically in male adolescent rats using the conditioned place preference (CPP) model. We found that CPP is observed after low dose nicotine injections when given to each rat of a pair that are together during conditioning whereas neither rewarding stimulus (i.e., nicotine injections or presence of another rat) supported CPP when given alone (Thiel et al, 2009, Bastle et al, 2016). We have also found that nicotine-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis is blunted in male and female adolescent rats given nicotine immediately before being placed into a cage with a same-sex partner compared to controls that were placed into the cage alone (Pentkowski et al, 2011).…”

“…Since initiation of nicotine use in humans typically occurs in a social setting (West et al, 1999, Baker et al, 2004, Geckova et al, 2005, Sussman, 2005), the use of social context during acquisition of nicotine self-administration is important and under-utilized in preclinical animal studies. Given that different neural circuits are activated in social versus isolated rodents (Insel, 1992, Young et al, 2001, Fritz et al, 2011a, El Rawas et al, 2012, Bastle et al, 2016), which may influence neural activity when exposed to drugs of abuse (Pentkowski et al, 2011, Bastle et al, 2016), future research aimed at understanding the neural mechanisms that underlie social influences on nicotine self-administration may have important implications for developing treatments for nicotine dependence.…”

Social influence of e-cigarette smoking prevalence on smoking behaviours among high-school teenagers: Microsimulation experiments

“…Some studies have indicated that social influence affects adolescents’ smoking behaviours via activating the reward system [39]. An experimental animal study with rats found that the interaction between social environment (peer existence) and nicotine uptake induces early gene expression in reward-related regions, suggesting that social influence enhances the neurobiological effect of nicotine by modifying the reward system to facilitate initiation and maintenance of nicotine preference [40]. Utility is an expression of reward valuation, and our model incorporates the utility function of smoking, which is affected by social influence and substance use experience.…”