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.

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.

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.

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.

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.

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.

Self-Administration of Smokeless Tobacco Products in Rats.

Objective: Preclinical abuse liability assessment is an essential component of tobacco regulatory science. The goal of this project was to evaluate the relative abuse liability of smokeless tobacco products in rats using aqueous extracts of those products. These extracts provide exposure to an extensive range of nicotine and non-nicotine tobacco constituents as occurs in humans.

Abuse liability assessment of an e-cigarette refill liquid using intracranial self-stimulation and self-administration models in rats.

Background: The popularity of electronic cigarettes (ECs) has increased dramatically despite their unknown health consequences. Because the abuse liability of ECs is one of the leading concerns of the Food and Drug Administration (FDA), models to assess it are urgently needed to inform FDA regulatory decisions regarding these products. The purpose of this study was to assess the relative abuse liability of an EC liquid compared to nicotine alone in rats.

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation.

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction.

Effects of nicotine and minor tobacco alkaloids on intracranial-self-stimulation in rats.

Background: While nicotine is the primary addictive compound in tobacco, other tobacco constituents including minor alkaloids (e.g., nornicotine, anabasine) may also contribute to tobacco addiction by mimicking or enhancing the effects of nicotine.

Animal models to assess the abuse liability of tobacco products: effects of smokeless tobacco extracts on intracranial self-stimulation.

Background: Preclinical models are needed to inform regulation of tobacco products by the Food and Drug Administration (FDA). Typically, animal models of tobacco addiction involve exposure to nicotine alone or nicotine combined with isolated tobacco constituents (e.g.