Increased Risky Choice and Reduced CHRNB2 Expression in Adult Male Rats Exposed to Nicotine Vapor

Abstract

While the cognitive enhancing effects of nicotine use have been well documented, it has also been shown to impair decision making. The goal of this study was to determine if exposure to nicotine vapor increases risky decision making. The study also aims to investigate possible long-term effects of nicotine vapor exposure on the expression of genes coding for cholinergic and dopaminergic receptors in brain. Thirty-two adult male Sprague Dawley rats were exposed to 24 mg/mL nicotine vapor or vehicle control, immediately followed by testing in the probability discounting task for 10 consecutive days. Fifty-four days after the 10-day vapor exposure, animals were sacrificed and expression of genes coding for the α4 and β2 cholinergic receptor subunits, and dopamine D1 and D2 receptors, were analyzed using RT-PCR. Exposure to nicotine vapor caused an immediate and transient increase in risky choice. Analyses of gene expression identified significant reductions in CHRNB2 and DRD1 in the nucleus accumbens core and CHRNB2 and DRD2 in the medial prefrontal cortex of rats previously exposed to nicotine vapor, relative to vehicle controls. Results provide data on the negative cognitive effects of nicotine vapor exposure and identify cholinergic and dopaminergic mechanisms that may affected with repeated use.

Keywords: cholinergic; dopaminergic; e-cigarette; nicotine; rat; risky choice.

Figure 1

Stability in the probability discounting task. (A) Rats maintained stable risk curves across baseline (BL) training days 31–35. (B) An effect of vehicle vapor exposure was observed on day 1 of exposure. Importantly, this effect was no longer seen after 6 days of exposure to vehicle vapor. * p < 0.05 when comparing average BL to first day of exposure to vapor vehicle (0 mg/mL D1).

Figure 2

Effects of 24 mg/mL nicotine vapor exposure on risky choice preference. (A) Nicotine vapor exposure increased risky choice during block 2, when the large reward had a 50% probability of delivery, on days 1, 2, 4, 9, and 10. No effect of treatment was observed on risky choice during (B) block 3, when the large reward had a 25% probability of delivery or (C) block 4, when the large reward had a 12.5% probability of delivery. * p < 0.05; ~ Bonferroni correction < 0.005.

Figure 3

Effects of 24 mg/mL nicotine vapor exposure on gene expression, normalized and relative to controls. (A) Significant reductions in gene expression were seen for CHRNB2 and DRD1 genes in nucleus accumbens core of rats previously exposed to nicotine vapor, relative to controls. (B) Significant reductions in gene expression were seen for CHRNB2 and DRD2 genes in medial prefrontal cortex of rats previously exposed to nicotine vapor, relative to controls. * p < 0.05.

Figure 4

Experimental Design. Schematics depicting (A) timeline for experimental procedures and (B) structure of probability discounting task. Task requires rat to choose between two levers. A press on one lever results in delivery of a small food reward with guaranteed delivery. A press on the other lever results in delivery of a large food reward with probability of delivery.