Nicotine Withdrawal Research Articles

Discrimination and insomnia: Examining depressive symptoms and nicotine withdrawal through a serial mediation model in a sample of smokers

Insomnia is a common sleep disorder associated with poor health outcomes. Individuals from racially underrepresented groups as well as women tend to report more severe insomnia symptoms, and frequent experiences of discrimination have been found to drive such disparities. Smokers commonly experience sleep problems since nicotine can alter the sleep-wake cycle. Discrimination is associated with increased nicotine dependence, and such discrimination may also intensify tobacco withdrawal, specifically mood and cognitive-related aspects of withdrawal. The potential impact of discrimination on withdrawal symptoms and related mood symptoms like depression may lead to increases in insomnia symptoms. However, no studies to date have evaluated the indirect association of discrimination with insomnia severity through nicotine withdrawal and depressive symptoms. Therefore, this cross-sectional survey of n = 110 non-Hispanic Black and White current smokers (48.2 % Black, 69.1 % women) investigated these associations through a serial mediation model. Controlling for race, gender, nicotine dependence levels, and income, multivariate analyses supported a significant indirect effect of discrimination on insomnia severity through depressive symptoms. Analyses supported the hypothesized serial mediation model whereby discrimination is positively associated with depressive symptoms, which in turn are linked to more severe nicotine withdrawal, leading to greater insomnia severity. Smokers encountering frequent experiences of discrimination might be at increased risk of suffering insomnia as a result of their increased depressive and withdrawal symptoms. Future work is necessary to understand the role of depressive symptoms in these associations as well as possible implications for smoking relapse and success of smoking cessation programs.

Nitric Oxide Linked to mGluR5 Upregulates BDNF Synthesis by Activating MMP2 in the Caudate and Putamen after Challenge Exposure to Nicotine in Rats.

Nitric oxide (NO) linked to glutamate receptors in the caudate and putamen (CPu) regulates neuroadaptation after drug exposure. Matrix-metalloproteinase (MMP), a Ca2+-dependent zinc-containing endopeptidase, increases mature brain-derived neurotrophic factor (BDNF) synthesis after drug exposure in the brain. The present study determined that NO synthesis linked to metabotropic glutamate receptor subtype 5 (mGluR5) stimulation after challenge exposure to nicotine activates MMP, which upregulates BDNF synthesis in the CPu. Subcutaneous injection of challenge nicotine (1.0 mg/kg) after repeated injections of nicotine (1.0 mg/kg/day) for 14 days and 7 days of nicotine withdrawal increased MMP2 activity and BDNF expression in the CPu of rats. These increases were prevented by the bilateral intra-CPu infusion of the mGluR5 antagonist, MPEP (0.1 nmol/side), the IP3 receptor antagonist, xestospongin C (0.004 nmol/side) or the neuronal nitric oxide synthase (nNOS) and NO inhibitor, Nω-propyl (0.1 nmol/side) prior to the challenge nicotine. Furthermore, bilateral intra-CPu infusion of the MMP2 inhibitor, OA-Hy (1 nmol/side) prevented the challenge nicotine-induced increase in the expression of BDNF. These findings suggest that elevation of NO synthesis linked to mGluR5 potentiates BDNF synthesis via activation of MMP2 after challenge exposure to nicotine in the CPu of rats.

Insula deep rTMS and varenicline for smoking cessation: A randomized control trial study protocol.

Background: Current approved therapies for smoking cessation have modest long-term effects for abstinence. The insular cortex has been identified by preclinical and clinical studies as a critical target for addiction treatment. Insula functions can be modulated non-invasively using brain stimulation. It is unknown if deep repetitive transcranial magnetic stimulation (rTMS) of the insula can improve smoking cessation of smokers trying to quit using varenicline. Methods: This will be a randomized, double-blind, sham-controlled clinical trial with 50 nicotine dependent smokers looking to quit. They will be randomly assigned to receive either active (10 Hz) or sham insula deep rTMS. Deep rTMS will be administered for 4 weeks (5 days/week). All participants will receive open label varenicline for 12 weeks. The primary outcome measure will be the 7-day point prevalence abstinence at the end of 12 weeks. The secondary outcomes will be Fagerström Test of Nicotine Dependence, Minnesota Nicotine Withdrawal Scale, Tiffany Questionnaire of Smoking Urges, expired carbon monoxide measurements, cigarettes smoked per day, point prevalence abstinence at end of 4 weeks, prolonged and continuous abstinence at 6 months. The measures will be collected throughout the 3-month treatment period as well as at the 6-month follow up. Discussion: This trial will test for the first time the impact of deep insula rTMS on smoking cessation in smokers treated with varenicline. This trial will use an H-coil specific to the insula, while previous studies have targeted both the insula and prefrontal cortex. This trial will inform on the utility to combine insula deep rTMS with varenicline to improve smoking abstinence rates. Clinical Trial Registration: Trial registered at https://clinicaltrials.gov/ct2/show/NCT04083144 (Identifier: NCT04083144).

Nicotine Replacement Therapy Does Not Reduce Headaches Following Subarachnoid Hemorrhage: A Propensity Score-Matched Study.

A significant number of patients admitted for aneurysmal subarachnoid hemorrhage (aSAH) are active smokers and are at risk of developing nicotine withdrawal symptoms (e.g., cravings, irritability, insomnia, headaches, etc.). This study aimed to evaluate the use of nicotine replacement therapy (NRT) regarding headache severity and analgesics consumption. A retrospective study was conducted using prospectively collected data from 2014 to 2019 in the neurointensive care unit of the Hospices Civils in Lyon, France. We performed a propensity score matching analysis. The covariables used were age, sex, initial World Federation of Neurosurgical Societies score, Hijdra sum score, and factors associated with pain following aSAH (history of chronic pain, anxiety, or depression). Smokers received NRT through a transdermal device. The primary end point was headache control. Secondary end points were mean numerical pain rating scale score and analgesics consumption. One hundred and fifty-five patients were included among 523 patients hospitalized for aSAH. Fifty-one patients underwent nicotine substitution and were matched to 51 unsubstituted patients. The headache control rate was not different between the two groups (43.1% vs. 31.4%, p = 0.736). The mean numeric pain rating scale score in the substituted group was 2.2 (1.1-3.5) and 2.4 (1.6-3.1) in the unsubstituted group (p = 0.533). The analgesics consumption (acetaminophen, tramadol, and morphine) was the same in the two groups. The use of NRT in the acute phase of aSAH does not seem to have an impact on the intensity of headaches or analgesics consumption.

The experience of nicotine dependence among adolescent smokers

A cigarette contains nicotine substance that can cause smokers to become dependent on nicotine. Smokers who are already addicted will experience withdrawal syndrome. The earlier age people smoke at, the higher level of dependence they have. The adverse effect of nicotine dependence is that smokers will find it difficult to stop smoking. This study aimed to investigate the experiences of adolescent smokers who are dependent on nicotine. This was a qualitative study conducted with a phenomenological approach. Data were collected through an in-depth interview with five informants who were selected through purposive sampling technique. Triangulation was employed to enhance the credibility of the study. Data were analyzed using a phenomenological approach. This study resulted in four main themes, namely: age to start smoking; the causes of smoking; perceptions of smoking; experience of smoking cessation. Conclusion that can be drawn for this study was smoking abstinence led to anxiety, decreased concentration and craving to cigarette. The smokers need to educate about the nicotine withdrawal symptoms that they can anticipate it when symptoms appeared.

OA10.06 An Unconventional Financial Incentive Based Feasibility Trial for Smoking Cessation

Financial incentive-based smoking cessation trials increased cessation rates from 6% to 16.3%. We adjusted our trial to address two major concerns regarding nicotine addiction. First, the constancy of nicotine withdrawal needs to be counteracted by a frequently given financial reward to offset cravings. Therefore, we increased the reward interval to weekly/biweekly. Second, commitment contracts produced favorable quitting rates but were not widely accepted. We created an experimental group that employs delayed rewards to mimic commitment contracts without their objectionable aspects.

Age-specific impacts of nicotine and withdrawal on hippocampal neuregulin signalling.

Smoking remains the leading cause of preventable death in the United States, with 87% of smokers starting before the age of 18. Age of initiation is a major predictive factor for smoking frequency and successful smoking cessation. People who initiate smoking during adolescences are 2.33 times more likely to become heavy smokers and half as likely to quit compared with smokers who started during adulthood. Additionally, schizophrenia, a disease state linked to altered neurodevelopment during adolescence, is a major predictive factor for smoking status. Smoking rates among people suffering from schizophrenia are between 60% and 90%. Interestingly, the Neuregulin Signalling Pathway (NSP), which plays an important role in neurodevelopment, is implicated in both schizophrenia and nicotine use disorder. Specifically, SNPS in neuregulin 3 (Nrg3) and Erb-B2 Receptor Tyrosine Kinase 4 (ErbB4) have been associated with smoking cessation outcomes and schizophrenia. Here, we examine the effects of chronic nicotine (18 mg/kg/day) and 24-h withdrawal on NSP gene expression in the hippocampus of adult (20-week-old) and adolescent (4-week-old) mice. We show that withdrawal from chronic nicotine decreased the expression of Erbb4 mRNA in the hippocampus of the adult mice but increased the expression of cytosolic Erbb4 protein in adolescent mice. Nrg3 mRNA and protein expression was not altered by chronic nicotine or withdrawal in the adult or adolescent cohorts, but Nrg3 mRNA and synaptosomal protein expression was lower in the adult withdrawal group when compared with their adolescent counterparts. These results highlight the age-specific effects of nicotine withdrawal on the NSP and may contribute to the lower quit rate and higher cigarette consumption of smokers who initiation during adolescences.

Mechanism of Electroacupuncture Analgesia on Nicotine Withdrawal-Induced Hyperalgesia in a Rat Model.

Purpose This study aimed to investigate the analgesic effect and mechanism of electroacupuncture (EA) in nicotine withdrawal-induced hyperalgesia rats. Methods Behavioral testing was conducted twice a week for 7 weeks during nicotine administration using von Frey filaments. Electroacupuncture at the bilateral “Zusanli” and “Taichong” points was applied daily for 3 days during nicotine withdrawal. Western blot analysis and immunohistology were used to determine expression levels of pain-related factors in the spinal cord and midbrain periaqueductal gray (PAG). Results Behavioral tests showed that electroacupuncture had a significant analgesic effect on nicotine withdrawal-induced hyperalgesic rats. Western blot results demonstrated that, in hyperalgesic rats, the expressions of nicotinic acetylcholine receptors (subunits: nAChR α7, α4, or β2) decreased in the spinal cord, nAChR α7, and β2 decreased in PAG. The proinflammatory factor cyclooxygenase 2 (COX2) and the activated microglia (ionized calcium-binding adaptor molecule 1, Iba1 positive cells) increased in the spinal cord and PAG compared to controls. After electroacupuncture treatment, nAChR α7 and nAChR β2 expressions increased significantly, and COX2 and Iba1 expressions decreased in the spinal cord. Compared with the nonelectroacupuncture nicotine withdrawal group, electroacupuncture stimulation increased the expression of nAChR α7 and nAChR α4 in the PAG of rats with electroacupuncture. Immunohistochemical results confirmed that electroacupuncture reversed nicotine withdrawal-induced changes in nAChR α7 positive neurons and Iba1-positive microglia in the dorsal horn of the spinal cord. Conclusion Electroacupuncture treatment has an analgesic effect on nicotine withdrawal-induced pain in nicotine-dependent rats. The mechanism of analgesia of the electroacupuncture treatment relates to the increased expression of nAChR α7 and nAChR β2 proteins in the spinal cord, nAChR α7 in the PAG, and decreased expression of Iba1 and COX2 protein in the spinal cord.

In Case You Haven't Heard…

Many years ago, then‐Surgeon General Everett Koop warned that nicotine is more addictive than heroin. That fateful day, in 1988, marked the beginning of what appeared to be a successful industry aimed at treating nicotine addiction. There were gums, patches, and more to help people stop smoking, which cost them a lot of money and possible future lung and other cancers. Now, we have vaping, including of nicotine, which at least is not combustible and, it is hoped, avoids the cancer problems. But it is still addictive. Ask any teenager, and you will learn that it's common in high school and college. Nicotine withdrawal is unpleasant. But there are still U.S. Food and Drug Administration (FDA)‐approved products to help. These are not vaping devices. With the FDA's current move to restrict the nicotine content of cigarettes, it's likely that there will be more demand for these products. For more information, go to https://www.fda.gov/consumers/consumer‐updates/want‐quit‐smoking‐fda‐approved‐and‐fda‐cleared‐cessation‐products‐can‐help.

Nicotine withdrawal as an unusual cause of terminal delirium.

Delirium is a neurocognitive and neuropsychiatric syndrome characterized by cognitive symptoms (eg, attention, perception, orientation, memory) and psychiatric symptoms (eg, hallucinations, delusions, agitation, apathy).[1][1],[2][2] Acute medical illness, trauma, surgery, substance use and

Switching from cigarettes to IQOS: A pilot examination of IQOS-associated reward, reinforcement, and abstinence relief

BackgroundIt is unknown whether IQOS-associated decreases in cigarette craving, nicotine withdrawal, greater subjective reward, and relative reinforcing value predict subsequent switching from cigarettes to IQOS products. MethodsNontreatment-seeking adult daily smokers (n = 33; 18–65 years old) completed a within-subject pilot study consisting of a baseline ad-lib smoking period (days 1–5), two laboratory visits (days 6–7), and a two-week period where participants switch from using cigarettes to using IQOS (days 8–21). Mixed-effect modelling estimated the percentage of baseline cigarette consumption replaced by daily IQOS HeatSticks used. Predictors of use included IQOS-associated reinforcement, subjective reward, and craving and withdrawal relief. ResultsIQOS use alleviated cigarette abstinence-associated craving (change=−14.22, p < .001) but did not alleviate withdrawal symptoms. Smokers initially substituted IQOS for 59% of their average daily cigarette consumption, increasing to 87% by switch period end (B=0.02 [95%CI=0.01, 0.03], p = .002). Neither subjective reward of IQOS nor relief of cigarette craving and withdrawal symptoms were predictive of this change. By study end, IQOS consumption was 124% of regular cigarette consumption among participants with a low reinforcing value of cigarettes relative to IQOS (β = 0.03 [95%CI=0.00, 0.06], p = .049). In contrast, participants with a higher reinforcing value of smoking replaced 76% of their cigarettes with IQOS. ConclusionsIQOS shows potential as an alternative to combustible cigarettes. However, IQOS use may result in dual-use for most smokers and increase tobacco consumption among a subgroup of smokers. These preliminary findings highlight the need for a larger investigation of the relationship between IQOS use and cigarette smoking.

Novel rapid-acting sublingual nicotine tablet as a cigarette substitution strategy

Current nicotine replacement products provide a much slower onset of nicotine delivery than cigarettes, and hence are only marginally effective at supplanting cigarette smoking. Therefore, more effective forms of nicotine replacement are needed. This initial investigation characterized the pharmacokinetic (PK) and subjective effects of a novel sublingual (SL) nicotine tablet designed to deliver nicotine more rapidly to the bloodstream of smokers. Study 1 (N = 6) characterized the pharmacokinetics of a 2mg nicotine SL tablet in comparison to an FDA-approved, marketed 2mg nicotine lozenge. Study 2 (N = 24) assessed subjective responses of smokers to a single use of a 1mg and 2mg SL tablet. Study 1 found that the time to maximum blood nicotine concentrations was significantly shorter for the SL tablet (14min) than for the lozenge (82min), and the initial rate of nicotine absorption was higher (0.4ng/mL*min vs. 0.0ng/mL*min), supporting the hypothesis that the SL tablet delivered nicotine more rapidly. Study 2 found that participants reported immediate relief of nicotine withdrawal symptoms after tablet administration, and craving reduction after the 2mg tablet approached the degree reported for their usual brands of cigarettes (4.2 vs. 4.6 on a 7-point scale). Other subjective responses showed the tablet to be an appealing alternative to smoking. The novel SL tablet studied shows promise as a nicotine substitution strategy for tobacco harm reduction and smoking cessation treatment. Additional studies are warranted to further investigate the potential of this new approach.

A BRIEF OVERVIEW OF DIFFERENT NICOTINE ADDICTION SCALES

Substance abuse is a serious public health problem across the world and is one of the biggest curses that modernsociety is facing. The assessment of nicotine addiction has been considered as a key topic as research into tobaccoaddiction progresses. Improved measurement may be required to make progress in tobacco research. The way nicotineaddiction is defined and assessed can have an impact on the findings and interpretations of studies and clinical trials.The Fagerström Tolerance Questionnaire (FTQ) and its shorter counterpart, the Fagerström Test for NicotineDependence (FTND), are the most well-known measures in terms of history and have been utilised in clinical andresearch contexts. The Fagerström scales, on the other hand, were designed to assess physical tolerance and thus donot assess several important aspects of nicotine dependence, such as cravings, subjective compulsion to smoke,nicotine withdrawal, behavioural saliency, or behavioural automaticity, which are frequently regarded as coreconstructs for dependence. Some evaluation instruments have been created in order to capture various features ofnicotine addiction. Each new iteration of these scaling algorithms improves on the previous one. The purpose of thisarticle is to provide a quick overview of several scales and to explore their properties.

Tobacco cigarette smokers who endorse greater intolerance for nicotine withdrawal also report more severe insomnia symptoms.

It has been suggested that nighttime nicotine withdrawal may help to explain why tobacco cigarette smokers are more likely than nonsmokers to experience clinically significant insomnia. There is also reason to believe that intolerance for withdrawal symptoms could play a role in withdrawal-related sleep disturbance. However, we are not aware of any previous research that examined whether smokers who endorse greater intolerance for smoking abstinence also report greater difficulty initiating and/or maintaining sleep. To address this question, 224 adult cigarette smokers (42.9% female, Mcigarettes per day = 21.3) completed the baseline portion of an experimental study that included assessment of current/historical smoking behavior, perceived intolerance for smoking abstinence, and insomnia severity and impact on functioning. The results indicated that, after accounting for general distress intolerance and sociodemographic factors, smokers who endorsed greater intolerance for nicotine withdrawal also reported greater insomnia severity and impact. Logistic regression further revealed that, for every 1-point increase in nicotine withdrawal intolerance scores, smokers were nearly twice as likely to score above threshold for clinically significant insomnia (p = .001). Collectively, these initial findings suggest that intolerance for nicotine withdrawal may warrant consideration as a potentially modifiable mechanistic factor in comorbid insomnia and nicotine/tobacco dependence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Prenatal Hypoxia Affects Nicotine Consumption and Withdrawal in Adult Rats via Impairment of the Glutamate System in the Brain.

The role of damaging factors in the prenatal period as a basis for drug addiction in offspring is of great interest. In this study, we aim at deciphering the effects and possible mechanisms of prenatal severe hypoxia (PSH) on predisposition to nicotine addiction in adult rats. In PSH rats, we found an increasing tendency to nicotine consumption in the two-bottle choice test. After 2weeks of chronic treatment with nicotine via osmotic minipump (9mg/kg per day), we assessed the symptoms of withdrawal in the conditioned place aversion test after mecamylamine (an antagonist of nicotinic acetylcholine receptors, nAChR) treatment. We showed that the mecamylamine-precipitated withdrawal aversion was stronger in the PSH group than in the control group. This suggests that PSH acts as a predisposing factor for developing nicotine addiction in adulthood. PSH rats also demonstrated an increased level of phosphorylated DARPP-32 protein (known as the relay for dopamine and glutamate signaling) at 34 threonine (pThr34DARPP-32) in relation to its total amount in the nucleus accumbens of the striatum (NAc). Meanwhile, no changes in both the content of dopamine in the mesolimbic pathway and the first type of dopamine receptors (DAR1) in NAc were found. The increased rate of DARPP-32 phosphorylation in adult PSH rats might result from excessive glutamatergic stimulation of the dopaminergic (DA) neurons of the ventral tegmental area (VTA) caused by activation of presynaptic nAChR by nicotine. This hypothesis is supported by the observed increase in VGluT2-positive terminals to Nurr1-positive neuronal bodies in VTA in PSH animals. Thus, the altered glutamate signaling phenotype might play a significant role in the development of PSH-related nicotine addiction.

Development of pulsed intravenous nicotine infusions as a model for inhaled nicotine in humans.

Although nicotine from cigarettes is delivered in puff-sized amounts, most preclinical and human intravenous (IV) nicotine studies have used bolus or continuous infusions. To determine the feasibility of a pulsed-nicotine infusion model in smokers. Following overnight abstinence, 12 adult smokers underwent 5 laboratory sessions. Using a crossover design, in each session, participants were assigned to 1 of 5 conditions: (1) high/fast: 1.0mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (2) high/slow: 1.0mg nicotine delivered over 20 pulsed-infusions; (3) low/fast: 0.2mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (4) low/slow: 0.2mg nicotine delivered over 20 pulsed-infusions; and (5) placebo: Saline delivered over 20 pulsed-infusions. Subjective drug effects, urges to smoke, nicotine withdrawal, and cognitive performance were measured in each session. Both the high/fast and high/slow conditions were associated with greater "head rush" and "high" (p < 0.05). The high/fast condition also provided greater suppression of urges to smoke and nicotine withdrawal (p < 0.05), indexed by the Questionnaire of Urges to Smoke-Brief, and the Minnesota Nicotine Withdrawal Scale, respectively. The high/fast and high/slow conditions produced greater increases in heart rate (p < 0.01) than saline. Finally, there were no main effects of dosing conditions on cognitive performance, indexed by the continuous performance test. These findings demonstrate the feasibility of pulsed-nicotine infusions to model nicotine delivery by smoking. This model could inform future studies testing novel smoking cessation therapies and tobacco regulatory studies testing the impact of nicotine reduction approaches.

Clinical approach to the treatment of e-cigarette use among adolescents

E-cigarette use remains a serious public health threat for adolescents in the United States. Pediatric providers can intervene early to prevent the adverse, and sometimes life-long, health consequences of e-cigarette use. This article reviews the clinical management of e-cigarette use among adolescents using the "Ask-Counsel-Treat" model. This model was recently introduced by the American Academy of Pediatrics to help pediatric healthcare providers manage e-cigarette screening, counseling, and treatment. Behavioral treatments for e-cigarette cessation can be delivered via multiple formats, including via text, in-person, or online. Additionally, pediatric healthcare providers may consider the off-label use of nicotine replacement therapy in individuals less than 18 years of age to alleviate some of the symptoms of nicotine withdrawal. Further research is needed to inform the design and implementation of effective e-cigarette cessation strategies for adolescents.

Role of Neuregulin 3‐ErbB4 Signaling in a Murine Model of Co‐Morbid Nicotine Dependence and Schizophrenia

According to the NIH, rates of nicotine dependence among patients with schizophrenia are at nearly 90%, compared to smoking rates of approximately 12% in the general population. Current research shows that variations in the gene for Neuregulin 3 (NRG3), a member of the EGF superfamily and the cognate ligand for ErbB4 receptors, are considered some of the strongest genetic links contributing to schizophrenia risk. Additionally, NRG3 protein and mRNA have been found to be highly enriched following chronic nicotine exposure and withdrawal. However, specific mechanisms underpinning NRG3’s association with both increased schizophrenia risk and increased nicotine withdrawal symptomology are unknown. In this ongoing experiment, we are testing the overall hypothesis that NRG3‐ErbB4 signaling effects on NMDA receptor function may provide a discrete, mechanistic link between nicotine dependence and schizophrenia.We plan to utilize a novel genetic mouse model of both nicotine dependence and schizophrenia in a multidimensional approach to study how NRG3 mediates nicotine withdrawal‐induced alterations on behavioral and molecular levels and how the alterations relate to schizophrenic‐like dysfunction. To first begin these investigations, we examined the behavioral and molecular baseline effects of nicotine and aripiprazole, a long‐acting atypical antipsychotic used to treat schizophrenia, in wildtype littermates. Animals treated chronically for nicotine and then undergoing spontaneous nicotine withdrawal were examined in the alternating Y‐maze, social interaction test, and open field test for efficacy in reducing behavioral endophenotypes common to both nicotine withdrawal and schizophrenia in our model. Following behavioral testing, PFC tissues were analyzed to determine mRNA and protein expression of factors in the NRG3 signaling pathway. Preliminary results show differential changes in mRNA expression associated with glutamatergic and serotonergic transmission in the mPFC, OFC, and hippocampus. Ongoing experiments will extend these studies to include time‐ and site‐specific genetic deletion of NRG3 in the PFC and compare these results to those derived in wildtype littermates. Our findings will provide insight into the underlying mechanisms linking the NRG3 signaling pathway and nicotine dependence, and may provide a novel link between nicotine use and its highly co‐morbid psychiatric disorder, schizophrenia. Findings from these highly translational studies may lead to novel therapeutic development for both nicotine dependence and schizophrenia.

Nicotine withdrawal after chronic exposure in adulthood blunts the ventilatory response to hypoxia in rats

Nicotine is one of the most addictive substances known, and it is estimated that 50.6 million US adults use nicotine in some form. It is well known that smoking, the most common form of nicotine exposure, alters lung structure and function. In contrast, the impact of chronic nicotine exposure during adulthood on neural structures involved in the control of breathing is largely unknown. In preliminary experiments in adult rats, we used plethysmography to study the effects of chronic nicotine exposure on the ventilatory response to hypoxia, which is a critical respiratory chemoreflex that enhances breathing and limits arterial O2 desaturation. Four weeks of chronic nicotine exposure through drinking water had no effect on the ventilatory response to a brief, 5‐ minute episode of hypoxia (10%) (Minute ventilation: One‐way ANOVA, Control vs Nicotine Exposure; P=0.6533). In contrast, nicotine exposed rats show a significantly blunted ventilatory response to hypoxia following 48 hours of nicotine withdrawal (Control vs Nicotine Withdrawal, P=0.0447). The reduced ventilatory response was due to a blunted increase in tidal volume (Amplitude: One‐way ANOVA, Control vs Nicotine Withdrawal; P=0.007), with a normal frequency response (Control vs Nicotine Withdrawal; P=0.2518. This has important clinical ramifications, as hypoxia is a commonly encountered medical complication, and withdrawal symptoms are often observed in hospitalized patients as it is common for them to abstain from smoking during periods of worsening health or in preparation for surgery.

P687. Sex-Dependent Effects of Progesterone on Nicotine Withdrawal and Neural Response to Smoking Cues During Brief Abstinence

Although exogenous progesterone may hold promise as a treatment for nicotine use disorders, it is unclear whether it is similarly effective in males and females. This study examined the effects of progesterone on nicotine use disorder comprehensively using behavioral, psychological, and neural measures in male and female smokers exposed to brief abstinence.