The Impact of Adolescent Alcohol Exposure on Nicotine Behavioral Sensitization in the Adult Male Neonatal Ventral Hippocampal Lesion Rat.

Emily D K Sullivan,Wilder T Doucette,Elise M Bragg,Liam N Locke,Angela M Henricks,Jibran Y Khokhar,Diana J Wallin

doi:10.3389/fnbeh.2021.760791

Abstract

Nicotine and alcohol use is highly prevalent among patients with serious mental illness, including those with schizophrenia (SCZ), and this co-occurrence can lead to a worsening of medical and psychiatric morbidity. While the mechanistic drivers of co-occurring SCZ, nicotine use and alcohol use are unknown, emerging evidence suggests that the use of drugs during adolescence may increase the probability of developing psychiatric disorders. The current study used the neonatal ventral hippocampal lesion (NVHL) rat model of SCZ, which has previously been shown to have enhanced nicotine behavioral sensitization and, following adolescent alcohol, increased alcohol consumption. Given how commonly alcohol is used by adolescents that develop SCZ, we used the NVHL rat to determine how exposure to adolescent alcohol impacts the development of nicotine behavioral sensitization in adulthood. Male Sprague-Dawley rats underwent the NVHL surgery or a sham (control) surgery and subsequently, half of each group was allowed to drink alcohol during adolescence. Nicotine behavioral sensitization was assessed in adulthood with rats receiving subcutaneous injections of nicotine (0.5 mg/kg) each day for 3 weeks followed by a nicotine challenge session 2 weeks later. We demonstrate that all groups of rats became sensitized to nicotine and there were no NVHL-specific increases in nicotine behavioral sensitization. We also found that NVHL rats appeared to develop sensitization to the nicotine paired context and that adolescent alcohol exposure blocked this context sensitization. The current findings suggest that exposure to alcohol during adolescence can influence behaviors that manifest in the adult NVHL rat (i.e., context sensitization). Interestingly, nicotine behavioral sensitization levels were not altered in the NVHL groups regardless of adolescent alcohol exposure in contrast to prior reports.

Highlights

Smoking is highly prevalent among patients with serious mental illness and this co-occurrence leads to medical and psychiatric morbidity (Green et al, 1999, 2008; Mallet et al, 2019) as well as an increased mortality risk (Tran et al, 2009; McGinty et al, 2012; Dickerson et al, 2018)
The results suggest that adolescent alcohol exposure from postnatal day (PD) 28–42 did not alter the amount of nicotine behavioral sensitization
When controlling for baseline differences in distance traveled, there were no differences in the amount of nicotine behavioral sensitization between neonatal ventral hippocampal lesion (NVHL) and sham rats, regardless of adolescent alcohol exposure

Summary

Introduction

Smoking is highly prevalent among patients with serious mental illness and this co-occurrence leads to medical and psychiatric morbidity (Green et al, 1999, 2008; Mallet et al, 2019) as well as an increased mortality risk (Tran et al, 2009; McGinty et al, 2012; Dickerson et al, 2018). In one investigation studying patients with SCZ or bipolar disorder, current smokers showed worse cognitive functioning and had poorer functional outcomes than past or never smokers. These effects were observed regardless of diagnosis, the patients with SCZ were twice as likely to be smokers compared to those with bipolar disorder (Depp et al, 2015). In a recent study, 31% of current smokers were readmitted to a psychiatric hospital within 1 year of discharge compared to 26% of never smokers (Kagabo et al, 2019) These studies indicate a correlation between smoking in patients with a serious mental illness and increased psychiatric morbidity and mortality

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Conclusion