Withdrawal from repeated nicotine vapor exposure increases somatic signs of physical dependence, anxiety-like behavior, and brain reward thresholds in adult male rats

Martínez, Michelle; Espinoza, Veronika E.; Garcia, Valeria; Uribe, Kevin P.; Negishi, Kenichiro; Estevao, Igor L.; Carcoba, Luis M.; O'Dell, Laura E.; Khan, Arshad M.; Mendez, Ian A.

doi:10.1016/j.neuropharm.2023.109681

Cited by 4 publications

(3 citation statements)

References 94 publications

(57 reference statements)

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“…While traditional models of chronic nicotine exposure generally report increased anxiety- and depression-like behaviors in response to nicotine cessation or abstinence 56 , 57 , chronic vapor-based exposure models demonstrate mixed findings. Some studies report that cessation results in increased anxiety-like behavior as measured by a novelty-suppressed feeding 20 or by the elevated plus maze 58 , 59 . However, others have reported findings similar to ours, whereby vapor-based nicotine exposure resulted in body-weight changes and physical signs of withdrawal but did not result in significant differences between groups during the open-field test 43 .…”

Section: Discussionmentioning

confidence: 99%

Effect of chronic vapor nicotine exposure on affective and cognitive behavior in male mice

Murdaugh,

Miliano,

Chen

et al. 2024

Sci Rep

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Nicotine use is a leading cause of preventable deaths worldwide, and most of those who attempt to quit will relapse. While electronic cigarettes and other electronic nicotine delivery systems (ENDS) were presented as a safer alternative to traditional cigarettes and promoted as devices to help traditional tobacco smokers reduce or quit smoking, they have instead contributed to increasing nicotine use among youths. Despite this, ENDS also represent a useful tool to create novel preclinical animal models of nicotine exposure that more accurately represent human nicotine use. In this study, we validated a chronic, intermittent, ENDS-based passive vapor exposure model in mice, and then measured changes in multiple behaviors related to nicotine abstinence. First, we performed a behavioral dose curve to investigate the effects of different nicotine inter-vape intervals on various measures including body weight, locomotor activity, and pain hypersensitivity. Next, we performed a pharmacokinetic study to measure plasma levels of nicotine and cotinine following chronic exposure for each inter-vape interval. Finally, we utilized a behavior test battery at a single dosing regimen that produces blood levels equivalent to human smokers in order to characterize the effects of chronic nicotine, vehicle, or passive airflow and identified nicotine-induced impairments in cognitive behavior.

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Section: Discussionmentioning

confidence: 99%

Effect of chronic vapor nicotine exposure on affective and cognitive behavior in male mice

Murdaugh,

Miliano,

Chen

et al. 2024

Sci Rep

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“…Two 30 min sessions were chosen in an attempt to model the multiple per day e-cigarette use seen per day in humans. Nicotine dependence has been shown to develop in as little as 7 to 14 days [13,14]. Vapor was delivered through a vapor inhalation system designed to deliver psychoactive substance vapor as previously described [15][16][17][18][19].…”

Section: Rat Exposure To E-cigarette Vapor Delivery Apparatusmentioning

confidence: 99%

Nicotine, THC, and Dolutegravir Modulate E-Cigarette-Induced Changes in Addiction- and Inflammation-Associated Genes in Rat Brains and Astrocytes

Kulbe,

Nguyen,

et al. 2023

Brain Sciences

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E-cigarette use has been marketed as a safer alternative to traditional cigarettes, as a means of smoking cessation, and are used at a higher rate than the general population in people with HIV (PWH). Early growth receptor 2 (EGR2) and Activity-Regulated Cytoskeleton-Associated Protein (ARC) have a role in addiction, synaptic plasticity, inflammation, and neurodegeneration. This study showed that 10 days of exposure to e-cigarette vapor altered gene expression in the brains of 6-month-old, male, Sprague Dawley rats. Specifically, the e-cigarette solvent vapor propylene glycol (PG) downregulated EGR2 and ARC mRNA expression in frontal cortex, an effect which was reversed by nicotine (NIC) and THC, suggesting that PG could have a protective role against NIC and cannabis dependence. However, in vitro, PG upregulated EGR2 and ARC mRNA expression at 18 h in cultured C6 rat astrocytes suggesting that PG may have neuroinflammatory effects. PG-induced upregulation of EGR2 and ARC mRNA was reversed by NIC but not THC. The HIV antiretroviral DTG reversed the effect NIC had on decreasing PG-induced upregulation of EGR2, which is concerning because EGR2 has been implicated in HIV latency reversal, T-cell apoptosis, and neuroinflammation, a process that underlies the development of HIV-associated neurocognitive disorders.

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“…Vapour models allow for the study of e-cigarette use parameters otherwise not possible, such as flavours, wattage, and salt/base ratio. Previous vapour findings have also shown that rodents will self-administer nicotine vapour [ 42 , 43 ], that nicotine vapour exposure leads to robust signs of physical dependence in adult male rats [ 44 ], and that nicotine vapour self-administration is potentiated by flavours [ 45 , 46 ], and nicotine salt [ 47 ]. Female rats also show greater increases in approach to the nicotine delivery port, and in adolescence, female nose pokes for nicotine vapour correlate with anxiety-like behaviour in the EPM [ 48 ].…”

Section: Introductionmentioning

confidence: 99%

Factors influencing JUUL e-cigarette nicotine vapour-induced reward, withdrawal, pharmacokinetics and brain connectivity in rats: sex matters

Frie,

McCunn,

Eed

et al. 2023

Neuropsychopharmacol.

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Though vaping likely represents a safer alternative to smoking, it is not without risks, many of which are not well understood, especially for vulnerable populations. Here we evaluate the sex- and age-dependent effects of JUUL nicotine vapour in rats. Following passive nicotine vapour exposures (from 59 mg/ml JUUL nicotine pods), rats were evaluated for reward-like behaviour, locomotion, and precipitated withdrawal. Pharmacokinetics of nicotine and its metabolites in brain and plasma and the long-term impact of nicotine vapour exposure on functional magnetic resonance imaging-based brain connectivity were assessed. Adult female rats acquired conditioned place preference (CPP) at a high dose (600 s of exposure) of nicotine vapour while female adolescents, as well as male adults and adolescents did not. Adult and adolescent male rats displayed nicotine vapour-induced precipitated withdrawal and hyperlocomotion, while both adult and adolescent female rats did not. Adult females showed higher venous and arterial plasma and brain nicotine and nicotine metabolite concentrations compared to adult males and adolescent females. Adolescent females showed higher brain nicotine concentration compared to adolescent males. Both network-based statistics and between-component group connectivity analyses uncovered reduced connectivity in nicotine-exposed rats, with a significant group by sex interaction observed in both analyses. The short- and long-term effects of nicotine vapour are affected by sex and age, with distinct behavioural, pharmacokinetic, and altered network connectivity outcomes dependent on these variables.

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Withdrawal from repeated nicotine vapor exposure increases somatic signs of physical dependence, anxiety-like behavior, and brain reward thresholds in adult male rats

Cited by 4 publications

References 94 publications

Effect of chronic vapor nicotine exposure on affective and cognitive behavior in male mice

Effect of chronic vapor nicotine exposure on affective and cognitive behavior in male mice

Nicotine, THC, and Dolutegravir Modulate E-Cigarette-Induced Changes in Addiction- and Inflammation-Associated Genes in Rat Brains and Astrocytes

Factors influencing JUUL e-cigarette nicotine vapour-induced reward, withdrawal, pharmacokinetics and brain connectivity in rats: sex matters

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