Nicotine bitartrate

Manufactured by Merck Group

Sourced in United States, United Kingdom

Nicotine bitartrate is a chemical compound that is used as a laboratory reagent. It is a salt formed by the combination of nicotine and tartaric acid. Nicotine bitartrate is a crystalline solid that is soluble in water and alcohol. It is commonly used in various scientific and research applications.

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Nicotine (271 citations) Nicotine hydrogen bitartrate (3 citations) (−)-Nicotine hydrogen bitartrate salt (2 citations)

30 protocols using nicotine bitartrate

Nicotine Bitartrate Administration Protocol

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Nicotine bitartrate (Sigma Chemical Co., St. Louis, MO) was dissolved into sterile saline. The pH of the solution was adjusted to 7.4 with dilute NaOH, and heparin (30 units/ml) was added to help maintain catheter patency. Nicotine doses are expressed as the base. Methohexital (Sigma Chemical Co., St. Louis, MO) was dissolved in sterile saline (0.1ml, 10 mg/ml, i.v.) and used to assess catheter patency.

Bunney P.E., Burroughs D., Hernandez C, & LeSage M.G. (2015). The effects of nicotine self-administration and withdrawal on concurrently available chow and sucrose intake in adult male rats. Physiology & behavior, 154, 49-59.

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Nicotine and Mecamylamine Dissolution and Preparation

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Nicotine bitartrate and mecamylamine (MEC) were obtained from Sigma Chemical Co. (St. Louis, MO) and dissolved in sterile saline. Whole Tobacco Alkaloid (WTA) EC refill liquid (Dark Honey Tobacco flavor in 10 ml vials) was obtained from Aroma E-Juice (http://www.aromaejuice.com, Scottsdale, AZ). According to the label, the refill liquid contained 80% vegetable glycerine (VG) and 20% propylene glycol (PG), and had a nicotine concentration of 24 mg/ml. The nicotine concentration was determined in each 10 ml vial of EC liquid used (see below), allowing dilution in saline to the nicotine concentrations required for the current studies. The pH of the solutions was adjusted to 7.4 with dilute NaOH or HCL, and heparin (30 units/ml) was added to help maintain catheter patency for the self-administration study. Nicotine and mecamylamine doses are expressed as the base and salt, respectively.

LeSage M., Staley M., Muelken P., Smethells J., Stepanov I., Vogel R., Pentel P, & Harris A. (2016). Abuse liability assessment of an e-cigarette refill liquid using intracranial self-stimulation and self-administration models in rats. Drug and alcohol dependence, 168, 76-88.

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Synthesis and Characterization of m-bromo PEP

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1-ethyl-4-(3-(bromo)phenyl)piperazine (m-bromo PEP; See Suppl. Fig. 1) was synthesized as described previously [29 (link)]. PNU-120596 was synthesized following the published procedure [45 ]. Fresh acetylcholine (ACh; Sigma-Aldrich, Saint-Louis, MO, USA) stock solutions were made each day of experimentation. PNU-120596 and m-bromo PEP stock solutions were prepared in dimethylsulfoxide (DMSO) (Sigma-Aldrich) and stored at −20 °C. Nicotine bitartrate (Sigma-Aldrich), mecamylamine (Tocris Bioscience, Bristol, UK), α-bungarotoxin (αBgt; Tocris), AR-R17779 (Tocris), recombinant human M-CSF (Sigma-Aldrich) and IFNγ (Cell Guidance Systems, Cambridge, UK) were prepared in PBS, stored at −20 °C. All working drug solutions were prepared fresh each day at the desired concentration from the stored stock. All doses are expressed as the free base of the drug.

Godin J.R., Roy P., Quadri M., Bagdas D., Toma W., Narendrula-Kotha R., Kishta O.A., Damaj M.I., Horenstein N.A., Papke R.L, & Simard A.R. (2019). A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE. Brain, behavior, and immunity, 87, 286-300.

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Continuous Nicotine Delivery in Mice

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As described previously (11 (link)), nicotine bitartrate (Sigma-Aldrich, St.Louis, MO, USA) in phosphate-buffered saline (PBS) (100mg/ml) or a solution containing PBS alone was freshly prepared and loaded into Alzet osmotic minipumps (model 1007D and model 2002, DurectCorporation, Cupertino, CA, USA) 12 hours before pump implantation. The pumps were implanted subcutaneously on the back of the mice and continuously delivered either PBS or nicotine salt at 0.39 mg of nicotine free base per mouse per day until the indicated days for sacrifice (7d, 12d, 16d or 22d). The pump implantation surgeries were done 2 days before MOG immunization.

Jiang W., St-Pierre S., Roy P., Morley B.J., Hao J, & Simard A.R. (2016). Infiltration of CCR2+Ly6Chigh Proinflammatory Monocytes and Neutrophils into the Central Nervous System Is Modulated by Nicotinic Acetylcholine Receptors in a Model of Multiple Sclerosis. The Journal of Immunology Author Choice, 196(5), 2095-2108.

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Intravenous Nicotine Self-Administration

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Nicotine hydrogen tartrate salt (nicotine bitartrate, Sigma, Natick, MA, USA) was dissolved in 0.9% saline (pH 7.4) and self-administered via an indwelling intravenous jugular catheter (0.03 mg/kg/100 µL infusion). Nicotine salt is preferred to the free base form for more stable storage and use during the experiments. Doses reported in this study are expressed as the free base concentrations.

Shankar K., Ambroggi F, & George O. (2022). Microstructural meal pattern analysis reveals a paradoxical acute increase in food intake after nicotine despite its long-term anorexigenic effects. Psychopharmacology, 239(3), 807-818.

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Synthesis and Characterization of m-bromo PEP

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Nicotinic Alkaloid Administration Protocol

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(−)-Nicotine bitartrate, (+/−) nornicotine, (+/−) anabasine, (+/−) myosmine, and (−)-cotinine were obtained from Sigma (St Louis, MO). (+/−) Anatabine was obtained from Toronto Research Chemicals, Inc. (Ontario, Canada). All drugs were prepared in sterile saline, adjusted to a pH of 7.4 using dilute NaOH, and administered s.c. in a volume of 1 ml/kg. All drug doses are expressed as the base.

Harris A.C., Tally L., Muelken P., Banal A., Schmidt C.E., Cao Q, & LeSage M.G. (2015). Effects of nicotine and minor tobacco alkaloids on intracranial-self-stimulation in rats. Drug and alcohol dependence, 153, 330-334.

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Nicotine Self-Administration Protocol

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Nicotine bitartrate (Sigma-Aldrich) was dissolved in 0.9% sterile saline (pH 7.4) and passed through a microfilter. A low dose (5 μg/kg/infusions) of nicotine was selected based on previous work demonstrating that this dose engenders rapid rates of acquisition, high levels of self-administration under extended access conditions, and robust levels of subsequent nicotine-seeking following 10 days of abstinence (Sanchez et al., 2013 (link); 2014 (link)). The dose is expressed as the free base weight and infusions were delivered at a rate of 0.1 ml/sec based on the animal’s weight. Nicotine solution was stored at 4 °C but was available at room temperature during self-administration sessions.

Sanchez V., Bakhti-Suroosh A., Chen A., Brunzell D.H., Erisir A, & Lynch W.J. (2019). Exercise during Abstinence Normalizes Ultrastructural Synaptic Plasticity Associated with Nicotine-Seeking following Extended Access Self-Administration. The European journal of neuroscience, 50(4), 2707-2721.

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Nicotine and Mecamylamine Delivery Protocol

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Nicotine bitartrate and mecamylamine hydrochloride (Sigma Chemical Co., St. Louis, MO) were dissolved in sterile saline. The pH of the nicotine solution was adjusted to 7.4 with dilute NaOH. Nicotine doses are expressed as the base. Nicotine was administered via osmotic minipump (see below). Mecamylamine was administered via s.c. injection at a volume of 1.0 ml/kg.

Muelken P., Schmidt C.E., Shelley D., Tally L, & Harris A.C. (2015). A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation. PLoS ONE, 10(12), e0144553.

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Naltrexone Effects on Substance Preferences

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Cocaine hydrochloride was received from the NIDA Drug Supply Program, nicotine bitartrate was purchased from Sigma Aldrich (St. Louis, MO, United States), and varenicline tartrate was purchased from Biotang (Lexington, MA, United States). Vehicle (0.97 mM HCl; salt equivalent of naltrexone HCl) and naltrexone HCl (N-3136; FW 377.9; Sigma-Aldrich) were used to pretreat animals prior to SOA preference testing. Benzaldehyde (#418099; 99.5%; Sigma-Aldrich; FW 106.12) was used to test for non-selective effects of naltrexone HCl. 2-nonanone (99%; CAS 821-55-6; FW 142.24; Arcos Organics) was used to show that animals could move away from the SOA target zone.

Engleman E.A., Steagall KB I.I., Bredhold K.E., Breach M., Kline H.L., Bell R.L., Katner S.N, & Neal-Beliveau B.S. (2018). Caenorhabditis elegans Show Preference for Stimulants and Potential as a Model Organism for Medications Screening. Frontiers in Physiology, 9, 1200.

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