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Exposure to smoke from high- but not low-nicotine cigarettes leads to signs of dependence in male rats and potentiates the effects of nicotine in female rats.

ABSTRACT: Nicotine is only mildly rewarding, but after becoming dependent, it is difficult to quit smoking. The goal of these studies was to determine if low-nicotine cigarettes are less likely to cause dependence and enhance the reinforcing effects of nicotine than regular high-nicotine cigarettes. Male and female rats were exposed to tobacco smoke with a low or high nicotine level for 35 days. It was investigated if smoke exposure affects the development of dependence, anxiety- and depressive-like behavior, and nicotine-induced behavioral sensitization. Smoke exposure did not affect locomotor activity in a small open field or sucrose preference. Mecamylamine precipitated somatic withdrawal signs in male rats exposed to smoke with a high level of nicotine, but not in male rats exposed to smoke with a low level of nicotine or in females. After cessation of smoke exposure, there was a small decrease in sucrose preference in the male rats, which was not observed in the females. Cessation of smoke exposure did not affect anxiety-like behavior in the large open field or the elevated plus maze test. Female rats displayed less anxiety-like behavior in both these tests. Repeated treatment with nicotine increased locomotor activity, rearing, and stereotypies. Prior exposure to smoke with a high level of nicotine increased nicotine-induced rearing in the females. These findings indicate that exposure to smoke with a low level of nicotine does not lead to dependence and does not potentiate the effects of nicotine. Exposure to smoke with a high level of nicotine differently affects males and females.

SUBMITTER: Chellian R

PROVIDER: S-EPMC7415730 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Exposure to smoke from high- but not low-nicotine cigarettes leads to signs of dependence in male rats and potentiates the effects of nicotine in female rats.

Chellian Ranjithkumar R Behnood-Rod Azin A Wilson Ryann R Wilks Isaac I Knight Parker P Febo Marcelo M Bruijnzeel Adriaan W AW

Pharmacology, biochemistry, and behavior 20200716

Nicotine is only mildly rewarding, but after becoming dependent, it is difficult to quit smoking. The goal of these studies was to determine if low-nicotine cigarettes are less likely to cause dependence and enhance the reinforcing effects of nicotine than regular high-nicotine cigarettes. Male and female rats were exposed to tobacco smoke with a low or high nicotine level for 35 days. It was investigated if smoke exposure affects the development of dependence, anxiety- and depressive-like behav ...[more]

PMID: 32681850

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Project description:IntroductionSmoking and the use of other nicotine-containing products is rewarding in humans. The self-administration of nicotine is also rewarding in male rats. However, it is unknown if there are sex differences in the reward-enhancing effects of nicotine self-administration and if the rewarding effects of nicotine change over time.MethodsRats were prepared with catheters and intracranial self-stimulation (ICSS) electrodes to investigate the effects of nicotine and saline self-administration on reward function. A decrease in thresholds in the ICSS procedure reflects an enhancement of reward function. The ICSS parameters were determined before and after the self-administration sessions from days 1 to 10, and after the self-administration sessions from days 11 to 15.ResultsDuring the first 10 days, there was no sex difference in nicotine intake, but during the last 5 days, the females took more nicotine than the males. During the first 10 days, nicotine self-administration did not lower the brain reward thresholds but decreased the response latencies. During the last 5 days, nicotine lowered the reward thresholds and decreased the response latencies. An analysis with the 5-day averages (days 1-5, 6-10, and 11-15) showed that the reward enhancing and stimulatory effects of nicotine increased over time. There were no sex differences in the reward-enhancing and stimulatory effects of nicotine. The nicotinic receptor antagonist mecamylamine diminished the reward-enhancing and stimulatory effects of nicotine.ConclusionThese findings indicate that the rewarding effects of nicotine self-administration increase over time, and there are no sex differences in the reward-enhancing effects of nicotine self-administration in rats.ImplicationsThis study investigated the rewarding effect of nicotine and saline self-administration in male and female rats. The self-administration of nicotine, but not saline, enhanced brain reward function and had stimulatory effects. The rewarding effects of nicotine increased over time in the males and the females. Despite that the females had a higher level of nicotine intake than the males, the reward-enhancing effects of nicotine self-administration were the same. These findings suggest that in new tobacco and e-cigarette users, nicotine's rewarding effects might increase quickly, and a higher level of nicotine use in females might not translate into greater rewarding effects.

Project description:ImportanceMenthol may make cigarette smoke less aversive and could lead youth to smoke more frequently and become more dependent on nicotine.ObjectiveTo assess the association of menthol use with cigarette smoking frequency and nicotine dependence (ND) among youth cigarettes users.Design, setting, and participantsThis cohort study used a pooled sample of cohorts of US youth (aged 12-17 years at their baseline and follow-up interviews) in the Population Assessment of Tobacco and Health Study (September 2013 to November 2019). Household interviews were conducted using audio computer-assisted self-interviews. US youth who were past-30-day cigarette smokers at any of wave 2 through wave 5, completed the preceding survey (eg, wave 2 past-30-day cigarette smokers completed wave 1), and indicated whether they used menthol cigarettes were eligible. The association of menthol use with smoking frequency and ND was estimated using inverse probability of treatment weighting adjusted mean differences (aMDs), adjusted risk ratios (aRRs), and corresponding 95% CIs. Data were analyzed from December 2021 to March 2022.ExposuresMenthol use and transitions in use (switching to or from menthol cigarettes).Main outcomes and measuresMain outcomes were the number of days smoked in the past 30 days, the risk of frequent smoking (smoking ≥20 days in the past 30 days), and symptoms of ND.ResultsThere were a total of 1492 observations among 1096 US youth cigarette smokers, of whom 49.4% were female, 67.2% were non-Hispanic White, and 28.7% were aged 12 to 14 years at their baseline survey (all percentages are weighted). Among those who switched from not smoking to smoking (61% of the sample), menthol use was associated with smoking on 3.1 additional days (aMD; 95% CI, 1.9 to 4.2 days), 59% higher risk of being a frequent smoker (aRR, 1.59; 95% CI, 1.23 to 2.06), and 10% higher ND scores (aMD, 1.09; 95% CI, 1.02 to 1.17). Switching from smoking menthol to smoking nonmenthol (vs maintaining menthol use) was associated with smoking on 3.6 fewer days (aMD; 95% CI, -6.3 to -0.9 days) and 47% lower risk of being a frequent smoker (aRR, 0.68; 95% CI, 0.50 to 0.92).Conclusions and relevanceThese findings suggest that the addition of menthol to cigarettes is associated with increased smoking frequency and ND among US youth.

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Exposure to smoke from high- but not low-nicotine cigarettes leads to signs of dependence in male rats and potentiates the effects of nicotine in female rats.

Publications

Exposure to smoke from high- but not low-nicotine cigarettes leads to signs of dependence in male rats and potentiates the effects of nicotine in female rats.

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