Magnitude and predictors of elasticity of demand for morphine are similar in male and female rats.

Introduction: Sex differences in vulnerability to opioid use disorder (OUD) have been reported in some clinical and preclinical studies, but findings are mixed and further research is needed in this area. The goal of this study was to compare elasticity of demand (reinforcement efficacy) in an i.v.

The role of β-Nicotyrine in E-Cigarette abuse liability I: Drug Discrimination.

Background: β-Nicotyrine (β-Nic) is a unique minor alkaloid constituent in electronic nicotine delivery systems (ENDS) that is derived from nicotine (Nic) degradation and can reach 25% of Nic concentrations in ENDS aerosol. β-Nic slows Nic metabolism and prolongs systemic Nic exposure, which may alter the discriminability of Nic. The present study sought to examine β-Nic has interoceptive effects itself, and if it alters the subjective effects ENDS products within a drug-discrimination paradigm.

Differential gene expression and chromatin accessibility in the medial prefrontal cortex associated with individual differences in rat behavioral models of opioid use disorder.

Opioid use disorder (OUD) is a neuropsychological disease that has a devastating impact on public health. Substantial individual differences in vulnerability exist, the neurobiological substrates of which remain unclear. To address this question, we investigated genome-wide gene transcription (RNA-seq) and chromatin accessibility (ATAC-seq) in the medial prefrontal cortex (mPFC) of male and female rats exhibiting differential vulnerability in behavioral paradigms modeling different phases of OUD: Withdrawal-Induced Anhedonia (WIA), Demand, and Reinstatement.

Substitutability of nicotine and sucrose in rats: A behavioral economic analysis.

Despite considerable evidence suggesting that sweet foods are a substitute for nicotine in humans, no formal behavioral economic analysis of this interrelationship has been conducted in nonhumans. The purpose of the present study was to examine this phenomenon in rats using concurrent schedules of sucrose pellet, chow pellet, and nicotine reinforcer delivery. Rats responded on separate levers that delivered sucrose pellets, chow pellets, or nicotine infusions under concurrent fixed-ratio (FR) 1 schedules for each commodity within a closed economy.

A TLR7/8 agonist increases efficacy of anti-fentanyl vaccines in rodent and porcine models.

Opioid use disorders (OUD) and overdose are public health threats worldwide. Widespread access to highly potent illicit synthetic opioids such as fentanyl is driving the recent rise in fatal overdoses. Vaccines containing fentanyl-based haptens conjugated to immunogenic carrier proteins offer a long-lasting, safe, and cost-effective strategy to protect individuals from overdose upon accidental or deliberate exposure to fentanyl and its analogs.

Cigarette Smoke Extract, but Not Electronic Cigarette Aerosol Extract, Inhibits Monoamine Oxidase and Produces Greater Acute Aversive/Anhedonic Effects Than Nicotine Alone on Intracranial Self-Stimulation in Rats.

Conventional tobacco cigarettes appear to have greater abuse liability than non-combusted products such as electronic cigarettes (ECs) and nicotine replacement therapy (NRT). This may be due to the higher levels of behaviorally active non-nicotine constituents [e.g.

Stimulus functions of nicotine.

Behavioral pharmacology has made vital contributions to the concepts and methods used in tobacco and other drug use research, and is largely responsible for the now generally accepted notion that nicotine is the primary component in tobacco that engenders and maintains tobacco use. One of the most important contributions of behavioral pharmacology to the science of drug use is the notion that drugs can act as environmental stimuli that control behavior in many of the same ways as other stimuli (e.g.

Attenuating nicotine's effects with high affinity human anti-nicotine monoclonal antibodies.

Use of nicotine-specific monoclonal antibodies (mAbs) to sequester and reduce nicotine distribution to brain has been proposed as a therapeutic approach to treat nicotine addiction (the basis of tobacco use disorder). A series of monoclonal antibodies with high affinity for nicotine (nic•mAbs) was isolated from B-cells of vaccinated smokers. Genes encoding 32 unique nicotine binding antibodies were cloned, and the mAbs expressed and tested by surface plasmon resonance to determine their affinity for S-(-)-nicotine.

Pharmacological mechanisms underlying the efficacy of antibodies generated by a vaccine to treat oxycodone use disorder.

Therapeutic vaccines offer a viable strategy to treat opioid use disorders (OUD) complementary to current pharmacotherapies. The candidate Oxy(Gly)-sKLH vaccine targeting oxycodone displayed pre-clinical proof of efficacy, selectivity and safety, and it is now undergoing clinical evaluation. To further support its implementation in the clinic, this study tested critical in vivo neuropsychopharmacological properties of the Oxy(Gly)-sKLH vaccine in rats.

The reinforcement threshold and elasticity of demand for nicotine in an adolescent rat model of depression.

Background: The Food and Drug Administration (FDA) is considering setting a nicotine standard for tobacco products to reduce their addictiveness. Such a standard should account for the apparent greater vulnerability to nicotine addiction in some subpopulations, such as adolescents with depression. The present study examined whether the reinforcement threshold and elasticity of demand (i.

β-Carbolines found in cigarette smoke elevate intracranial self-stimulation thresholds in rats.

Identifying novel constituents that contribute to tobacco addiction is essential for developing more effective treatments and informing FDA regulation of tobacco products. While preclinical data indicate that monoamine oxidase (MAO) inhibitors can have abuse liability or potentiate the addiction-related effects of nicotine, most of these studies have used clinical MAO inhibitors (e.g.

Higher anhedonia during withdrawal from initial opioid exposure is protective against subsequent opioid self-administration in rats.

Rationale: Understanding factors contributing to individual differences in vulnerability to opioid addiction is essential for developing more effective preventions and treatments, yet few reliable behavioral predictors of subsequent opioid self-administration have been identified in rodents. Sensitivity to the acute effects of initial drug exposure predicts later addiction vulnerability in both humans and animals, but the relationship between sensitivity to withdrawal from initial drug exposure and later drug use vulnerability is unclear.

Objective: The goal of the current study was to evaluate whether the degree of anhedonia experienced during withdrawal from early opioid exposure predicts subsequent vulnerability to opioid self-administration.

Flavor-specific enhancement of electronic cigarette liquid consumption and preference in mice.

Background: The use of electronic cigarettes has increased over the past decade. To determine how the abuse liability of electronic cigarette liquids (e-liquids) differs from nicotine alone, and to determine the impact of flavor, we compared nicotine-containing fruit- and tobacco-flavored e-liquids, and their nicotine-free versions, to nicotine alone in mouse models of oral consumption, reward and aversion.

Methods: Adult male C57BL/6 J mice voluntarily consumed oral nicotine, equivalent nicotine concentrations of fruit- and tobacco-flavored e-liquid, and equivalent dilutions of the nicotine-free versions in 2-bottle choice tests.

Comparison of the Relative Abuse Liability of Electronic Cigarette Aerosol Extracts and Nicotine Alone in Adolescent Rats: A Behavioral Economic Analysis.

Characterizing the determinants of the abuse liability of electronic cigarettes (ECs) in adolescents is needed to inform product regulation by the United States Food and Drug Administration (FDA). We recently reported that Vuse Menthol EC aerosol extract containing nicotine and a range of non-nicotine constituents (e.g.

Non-nicotine constituents in e-cigarette aerosol extract attenuate nicotine's aversive effects in adolescent rats.

Background: Development of preclinical methodology for evaluating the abuse liability of electronic cigarettes (ECs) in adolescents is urgently needed to inform FDA regulation of these products. We previously reported reduced aversive effects of EC liquids containing nicotine and a range of non-nicotine constituents (e.g.

Propylene glycol, a major electronic cigarette constituent, attenuates the adverse effects of high-dose nicotine as measured by intracranial self-stimulation in rats.

Background: Non-nicotine tobacco constituents may contribute to the abuse liability of tobacco products. We previously reported that electronic cigarette (EC) refill liquids containing nicotine and a range of non-nicotine constituents attenuated the anhedonic/aversive effects of nicotine in an intracranial self-stimulation (ICSS) model. The alcohol propylene glycol (PG) is a primary ingredient in these and other EC liquids, yet its abuse potential has not been established.

Status and Future Directions of Preclinical Behavioral Pharmacology in Tobacco Regulatory Science.

Behavioral pharmacology is a branch of the experimental analysis of behavior that has had great influence in drug addiction research and policy. This paper provides an overview of recent behavioral pharmacology research in the field of tobacco regulatory science, which provides the scientific foundation for the Food and Drug Administration Center for Tobacco Products (FDA CTP) to set tobacco control policies. The rationale and aims of tobacco regulatory science are provided, including the types of preclinical operant behavioral models it deems important for assessing the abuse liability of tobacco products and their constituents.

The nicotine-degrading enzyme NicA2 reduces nicotine levels in blood, nicotine distribution to brain, and nicotine discrimination and reinforcement in rats.

Background: The bacterial nicotine-degrading enzyme NicA2 isolated from P. putida was studied to assess its potential use in the treatment of tobacco dependence.

Results: Rats were pretreated with varying i.

A Bayesian hierarchical model for demand curve analysis.

Drug self-administration experiments are a frequently used approach to assess the abuse liability and reinforcing property of a compound. It has been used to assess the abuse liabilities of various substances such as psychomotor stimulants and hallucinogens, food, nicotine, and alcohol. The demand curve generated from a self-administration study describes how demand of a drug or non-drug reinforcer varies as a function of price.

Substitutability of nicotine alone and an electronic cigarette liquid using a concurrent choice assay in rats: A behavioral economic analysis.

Background: For the Food and Drug Administration to effectively regulate tobacco products, the contribution of non-nicotine tobacco constituents to the abuse liability of tobacco must be well understood. Our previous work compared the abuse liability of electronic cigarette refill liquids (EC liquids) and nicotine (Nic) alone when each was available in isolation and found no difference in abuse liability (i.e.

Effects of nicotine-containing and "nicotine-free" e-cigarette refill liquids on intracranial self-stimulation in rats.

Background: Animal models are needed to inform FDA regulation of electronic cigarettes (ECs) because they avoid limitations associated with human studies. We previously reported that an EC refill liquid produced less aversive/anhedonic effects at a high nicotine dose than nicotine alone as measured by elevations in intracranial self-stimulation (ICSS) thresholds, which may reflect the presence of behaviorally active non-nicotine constituents (e.g.

Locomotor activity does not predict individual differences in morphine self-administration in rats.

Understanding factors contributing to individual differences in opioid addiction vulnerability is essential for developing more effective preventions and treatments. Sensation seeking has been implicated in addiction to several drugs of abuse, yet its relationship with individual differences in opioid addiction vulnerability has not been well established. The primary goal of this study was to evaluate the relationship between locomotor activity in a novel environment, a preclinical model of sensation-seeking, and individual differences in acquisition of i.

Consortium on Methods Evaluating Tobacco: Research Tools to Inform US Food and Drug Administration Regulation of Snus.

Introduction: The US Food and Drug Administration (FDA) has purview over tobacco products. To set policy, the FDA must rely on sound science, yet most existing tobacco research methods have not been designed to specifically inform regulation. The NCI and FDA-funded Consortium on Methods Evaluating Tobacco (COMET) was established to develop and assess valid and reliable methods for tobacco product evaluation.

Similar precipitated withdrawal effects on intracranial self-stimulation during chronic infusion of an e-cigarette liquid or nicotine alone.

The FDA recently extended their regulatory authority to electronic cigarettes (ECs). Because the abuse liability of ECs is a leading concern of the FDA, animal models are urgently needed to identify factors that influence the relative abuse liability of these products. The ability of tobacco products to induce nicotine dependence, defined by the emergence of anhedonia and other symptoms of nicotine withdrawal following cessation of their use, contributes to tobacco abuse liability.