Characterization of a novel oronasal-restricted nicotine vaping self-administration model in mice.

Nicotine use remains one of the leading causes of preventable deaths in the United States and, while the prevalence of combustible cigarette use has declined over the past few years, the popularity of electronic nicotine delivery systems continues to rise. Vaping is not without risks, and its long-term effects, particularly in vulnerable populations, remain largely unknown. This study introduces a novel, oronasal-restricted, nicotine vapor self-administration mouse model to investigate the impact of nicotine concentration, genotype, sex, and age on self-administration and behavioral response to nicotine.

Investigating the role of nicotinic acetylcholine receptors in menthol's effects in mice.

The use of menthol in tobacco products has been linked to an increased likelihood of developing nicotine dependence. The widespread use of menthol can be attributed to its unique sensory characteristics; however, emerging evidence suggests that menthol also alters sensitivity to nicotine through modulation of nicotinic acetylcholine receptors (nAChRs). Nicotinic subunits, such as β2 and α5, are of interest due to their implications in nicotine reward, reinforcement, intake regulation, and aversion.

Impact of tobacco flavoring on oral nicotine consumption in C57BL/6J mice.

Background: The continued use of flavors in tobacco products has been a prominent factor in their popularity, yet little is known regarding their role in nicotine dependence. This study aimed to investigate the impact of tobacco flavoring on oral nicotine consumption in mice using the two-bottle choice (2BC) test and assessed the potential impact of age and sex in their interactions.

Methods: Adolescent and adult male and female C57BL/6J mice were used.

Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice.

Background: Because of their implications in several pathological conditions, α4β2* nicotinic acetylcholine receptors (nAChRs) are potential targets for the treatment of nicotine dependence, pain, and many psychiatric and neurodegenerative diseases. However, they exist in various subtypes, and finding selective tools to investigate them has proved challenging. The nicotinic receptor agonist, 5-iodo-A-85380 (5IA), has helped in delineating the function of β2-containing subtypes in vitro; however, much is still unknown about its behavioral effects.

Genotypic Differences in the Effects of Menthol on Nicotine Intake and Preference in Mice.

Menthol has been shown to exacerbate elements of nicotine addiction in humans and rodents; however, the mechanisms mediating its effects are not fully understood. This study examined the impact of genetic factors in menthol's effects on oral nicotine consumption by comparing two inbred mouse strains with differing sensitivities to nicotine. C57BL/6J (B6J) mice are nicotine-preferring, while DBA/2J (D2J) mice are not.

Potentiation of (α4)2(β2)3, but not (α4)3(β2)2, nicotinic acetylcholine receptors reduces nicotine self-administration and withdrawal symptoms.

The low sensitivity (α4)3(β2)2 (LS) and high sensitivity (α4)2(β2)3 (HS) nAChR isoforms may contribute to a variety of brain functions, pathophysiological processes, and pharmacological effects associated with nicotine use. In this study, we examined the contributions of the LS and HS α4β2 nAChR isoforms in nicotine self-administration, withdrawal symptoms, antinociceptive and hypothermic effects. We utilized two nAChR positive allosteric modulators (PAMs): desformylflustrabromine (dFBr), a PAM of both the LS and HS α4β2 nAChRs, and CMPI, a PAM selective for the LS nAChR.

Impact of menthol on nicotine intake and preference in mice: Concentration, sex, and age differences.

Menthol has been shown to contribute to the appeal of tobacco products in humans. However, factors such as sex, age and menthol concentration remain unclear in the interaction between menthol and nicotine. To understand these factors, we utilized a mouse model to determine the impact of menthol on oral nicotine consumption.

Examining the Effects of (α4)3(β2)2 Nicotinic Acetylcholine Receptor-Selective Positive Allosteric Modulator on Acute Thermal Nociception in Rats.

Neuronal nicotinic acetylcholine receptor (nAChR)-based therapeutics are sought as a potential alternative strategy to opioids for pain management. In this study, we examine the antinociceptive effects of 3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1-pyrazol-4-yl)isoxazole (CMPI), a novel positive allosteric modulator (PAM), with preferential selectivity to the low agonist sensitivity (α4)3(β2)2 nAChR and desformylflustrabromine (dFBr), a PAM for α4-containing nAChRs. We used hot plate and tail flick tests to measure the effect of dFBr and CMPI on the latency to acute thermal nociceptive responses in rats.

Inhibition of monoacylglycerol lipase reduces nicotine reward in the conditioned place preference test in male mice.

Nicotine, the primary psychoactive component in tobacco, plays a major role in the initiation and maintenance of tobacco dependence and addiction, a leading cause of preventable death worldwide. An essential need thus exists for more effective pharmacotherapies for nicotine-use cessation. Previous reports suggest that pharmacological and genetic blockade of CB1 receptors attenuate nicotine reinforcement and reward; while exogenous agonists enhanced these abuse-related behaviors.

C57BL/6 Substrain Differences in Pharmacological Effects after Acute and Repeated Nicotine Administration.

Tobacco smoking is the major cause of disability and death in the United States and around the world. In addition, tobacco dependence and addiction express themselves as complex behaviors involving an interplay of genetics, environment, and psychological state. Mouse genetic studies could potentially elucidate the novel genes and/or gene networks regulating various aspects of nicotine dependence.