Developing a model of limited-access nicotine consumption in C57Bl/6J mice

Abstract

Although United States smoking rates have been on the decline over the past few decades, cigarette smoking still poses a critical health and economic threat. Very few treatment options for smoking exist, and many of them do not lead to long-term abstinence. Preclinical models are necessary for understanding the effects of nicotine and developing treatments. Current self-administration models of nicotine intake may require surgical procedures and often result in low levels of intake. Further, they do not lend themselves to investigating treatments. The current study sought to develop a limited-access model of nicotine intake using the Drinking-in-the-Dark paradigm, which results in high levels of binge-like ethanol consumption that can be pharmacologically manipulated. The present study found that mice will consume nicotine under a range of parameters. Intakes under the preferred condition of 0.14 mg/ml nicotine in 0.2% saccharin reached over 6 mg/kg in two hours and were reduced by an injection of R(+)-baclofen. Mecamylamine did not significantly affect nicotine consumption. As nicotine and ethanol are often co-abused, nicotine intake was also tested in the presence of ethanol. When presented in the same bottle, mice altered nicotine intake under various concentrations to maintain consistent levels of ethanol intake. When nicotine and ethanol were presented in separate bottles, mice greatly reduced their nicotine intake while maintaining ethanol intake. In conclusion, these studies characterize a novel model of limited-access nicotine intake that can be pharmacologically manipulated.

Electronic Nicotine Vapor Exposure Produces Differential Changes in Central Amygdala Neuronal Activity, Thermoregulation and Locomotor Behavior in Male Mice

“…A voluntary route of nicotine delivery is oral consumption with bottle choice which showed nicotine-induced hypothermic and locomotor effects (DeBaker et al, 2020;Kasten et al, 2016;O'Rourke et al, 2016). However, this model of nicotine exposure does not replicate human consumption of nicotine and raises questions regarding taste preference when paired with other substances like sucrose.…”

“…Route of administration of nicotine is an important determining factor in the timing and magnitude of the reinforcing effects as well as the behavioral effects of nicotine exposure. In previous studies nicotine has been administered through experimenter-delivered injections ( Kasten et al, 2016 ) or subcutaneous minipumps ( LeSage et al, 2002 ). These models provide the benefit of standardized serum nicotine levels; however, these have limitations related to surgery and/or injection induced stress.…”

“…These models provide the benefit of standardized serum nicotine levels; however, these have limitations related to surgery and/or injection induced stress. A voluntary route of nicotine delivery is oral consumption with bottle choice which showed nicotine-induced hypothermic and locomotor effects ( Kasten et al, 2016 ; O’Rourke et al, 2016 ; DeBaker et al, 2020 ). However, this model of nicotine exposure does not replicate human consumption of nicotine and raises questions regarding taste preference when paired with other substances like sucrose.…”

Suppressing Effect of Baclofen on Multiple Alcohol-Related Behaviors in Laboratory Animals

“…In the “DID” studies, systemic administration of doses of R(+)-baclofen in the 5–10 mg/kg range markedly reduced alcohol intake in C57BL/6J mice ( 18 , 25 ), selectively bred High Alcohol Preferring 1 (HAP1) mice ( 18 ), and High DID (HDID) mice (selectively bred for high alcohol drinking under the DID regimen) ( 26 ). When tested in the SHAC procedure, baclofen (2.5 and 5 mg/kg, i.p.)…”

Therapeutic challenges for concurrent ethanol and nicotine consumption: naltrexone and varenicline fail to alter simultaneous ethanol and nicotine intake by female alcohol-preferring (P) rats

“…According to European standards, there are no known biological consequences of infusing nicotine into alcoholic solutions. Therefore, recently developed animal models of concurrent alcohol and nicotine oral consumption are ecologically valid and that validity is increasing in relevance (Hauser et al 2012b;Kasten et al 2016).…”