Nicotine-like behavioral effects of the minor tobacco alkaloids nornicotine, anabasine, and anatabine in male rodents.

Caine, S. Barak; Collins, Gregory T.; Thomsen, Morgane; Wright, Curtis; Lanier, Ryan K.; Mello, Nancy K.

doi:10.1037/a0035749

Cited by 57 publications

(64 citation statements)

References 55 publications

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“…Public Health Service, 1988). Rather, they were chosen based on their behavioral effects reported in other animal models of tobacco addiction and to establish the effective dose range in the present model (Caine et al, 2014; Dwoskin et al, 1999; Goldberg et al, 1989; Hall et al, 2014; Stolerman et al, 1995, 1984). Doses and pretreatment time were also based on a pilot study examining acute effects of these minor alkaloids on ICSS (data not shown).…”

Section: Methodsmentioning

confidence: 99%

“…To this end, the current study evaluated the acute effects of nicotine and the minor alkaloids nornicotine, anabasine, myosmine, anatabine, and cotinine on ICSS thresholds. Although nornicotine has been studied most extensively (e.g., Bardo et al, 1999; Dwoskin et al, 1999; Green et al, 2000), all of these minor alkaloids can produce behavioral effects under some conditions (Caine et al, 2014; Clemens et al, 2009; Goldberg et al, 1989; Hall et al, 2014; Pratt et al, 1983; Stolerman et al, 1995; Stolerman et al, 1984). …”

Section: Introductionmentioning

confidence: 99%

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

Harris¹,

Tally²,

Muelken³

et al. 2015

Drug and Alcohol Dependence

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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. Further evaluating the behavioral effects of minor alkaloids is essential for understanding their impact on tobacco addiction and informing development of tobacco product standards by the FDA. Methods This study compared the addiction-related effects of nicotine and the minor alkaloids nornicotine, anabasine, myosmine, anatabine, and cotinine on intracranial self-stimulation (ICSS) thresholds in rats. Results Acute injection of nicotine produced reinforcement-enhancing (ICSS threshold-decreasing) effects at low to moderate doses, and reinforcement-attenuating/aversive (ICSS threshold-increasing) effects at high doses. Nornicotine and anabasine produced similar biphasic effects on ICSS thresholds, although with lower potency compared to nicotine. Myosmine only elevated ICSS thresholds at relatively high doses, while anatabine and cotinine did not influence ICSS thresholds at any dose. None of the alkaloids significantly influenced ICSS response latencies, indicating a lack of nonspecific motoric effects. Conclusions These findings indicate that some minor tobacco alkaloids can either fully (nornicotine, anabasine) or partially (myosmine) mimic nicotine’s addiction-related effects on ICSS, albeit at reduced potency. These findings emphasize the need for further study of the abuse potential of minor alkaloids, including evaluation of their effects when combined with nicotine and other tobacco constituents to better simulate tobacco exposure in humans. Such work is essential for informing FDA regulation of tobacco products and could also lead to the development of novel pharmacotherapies for tobacco addiction.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Harris¹,

Tally²,

Muelken³

et al. 2015

Drug and Alcohol Dependence

View full text Add to dashboard Cite

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“…These results are consistent with those of a recent study in which intraperitoneal injection of similarly high doses of anatabine produced severe tremors and death in mice. 19 At a non-toxic dose of 1 mg/kg, anatabine increased activity across the entire session; however, the 10 mg/kg dose produced significant reductions in activity during the first 10 min of the session. When combined with the observations of overt behavior, the locomotor data suggest that behaviorally effective doses of anatabine may be relatively close to doses with acute toxicity (i.e., a narrow "therapeutic" index).…”

Section: Discussionmentioning

confidence: 99%

“…self-administration procedures, but was not reinforcing itself. [18][19][20] In summary, nicotine, cotinine, myosmine and anatabine produced distinctive patterns of effects on locomotor activity that were timeand dose-dependent. Nicotine and cotinine proved to be the most potent constituents (with lowest effective doses of 0.1 mg/kg) whereas the lowest effective doses of anatabine and myosmine were 1 mg/kg and 10 mg/kg, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…enhanced nicotine-induced stimulation of locomotor activity in rats and acted synergistically with other tobacco plant alkaloids to increase activity. 15 In mice trained to discriminate nicotine from vehicle, anatabine substituted for nicotine, but also partially attenuated nicotine's discriminative stimulus effects, 19 an effect attributed to its ability to serve as a full agonist at α4β2 nicotinic acetylcholine receptors. 19 In both rats and rhesus monkeys, anatabine attenuated the reinforcing effects of nicotine in i.v.…”

Section: Discussionmentioning

confidence: 99%

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Determination of Behaviorally Effective Tobacco Constituent Doses in Rats

Wiley

Marusich

Thomas

et al. 2014

Nicotine & Tobacco Research

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IntroductionTobacco use continues to be the leading preventable cause of premature deaths in the United States, with over 400,000 deaths per year attributed to cigarette smoking. 1 While nicotine is the primary tobacco constituent responsible for addiction, many of the other over 8,400 identified tobacco constituents, 2 including alkaloids, flavor additives, β-carbolines, and monoamine oxidase inhibitors, may also affect use and dependence. 3 Given the sparse knowledge about the in vivo pharmacology of most of these constituents, the objective of this study was to examine the effects on locomotor activity of anatabine and myosmine (two alkaloids that are present in larger quantities in tobacco products, including e-cigarettes; Etter, Zäther, and Svensson 4 ; Jacob et al. 5 ), cotinine (common tobacco constituent and a metabolite of nicotine; Jacob et al. 5 ) and nicotine (for comparison purposes). Nicotine doses (0.1-0.8 mg/kg, subcutaneous [s.c.]) were chosen based upon literature review, which showed that acute doses within this range affected locomotor activity, produced AbstractIntroduction: While nicotine has been established as the primary addictive drug that promotes tobacco use, recent peer-reviewed studies suggest that tobacco smoke contains additional chemical constituents that may have addictive potential. Additional research is necessary to determine the addictive potential of these tobacco constituents individually and in combination with tobacco smoke condensate; however, the behaviorally effective constituent doses necessary to conduct such studies are unclear. The primary objective of this study was to conduct behavioral studies in adult rats to determine the relevant behaviorally effective doses of the tobacco constituents, cotinine, myosmine, and anatabine to be used in future studies assessing the addictive potential of these compounds. Methods: Separate groups of adult male Sprague Dawley rats were treated with vehicle, nicotine, or various doses of cotinine, mysomine, or anatabine. Effects on locomotor activity were measured in 10-min bins for 60 min. Results: Nicotine (0.8 mg/kg) produced a biphasic effect on locomotor activity, with hypoactivity during the first 10 min and hyperactivity at 40-50 min. In contrast, cotinine (0.1 mg/kg) and myosmine (10-50 mg/kg) decreased activity without a later increase. Anatabine significantly increased locomotor activity at 1 mg/kg, but decreased it at 10 mg/kg. Prominent effects on overt behavior were observed at anatabine doses of 10 mg/kg and above. Conclusion: Nicotine, cotinine, myosmine, and anatabine produced distinct time-and dose-dependent patterns of effects on locomotor activity. Results from the study will aid in the selection of relevant doses for future studies assessing the addictive potential of these non-nicotine tobacco constituents.

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Multiple analyses of main flavor components in reconstituted tobacco and transfer behavior of their key substances during heating

Shi,

Yang,

Zhang

et al. 2024

J of Separation Science

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Reconstituted tobacco (RT) is a product made by reprocessing tobacco waste, experiencing a growing demand for heat‐not‐burn products. The purpose of this study is to analyze the main flavor ingredients in RT aerosol, as well as the transfer behavior of key flavor substances from substrates to aerosol and the concentrations of these compounds in the substrate after heating. First, we demonstrated that the odor of four RT aerosol samples could be distinguished using an electronic nose. Through non‐targeted analysis, 93 volatile compounds were detected by gas chromatography‐mass spectrometry, and 286 non/semi‐volatile compounds were identified by ultra‐high‐performance liquid electrophoresis chromatography‐mass spectrometry in aerosol. Furthermore, we found that the formation of RT aerosol involves primarily evaporation and distillation, however, the total content delivered from unheated RT samples to aerosol remains relatively low due to compound volatility and cigarette filtration. Thermal reactions during heating indicated the pyrolysis of chlorogenic acid to generate catechol and resorcinol, while Maillard reactions involving glucose and proline produced 2,3‐dihydro‐3,5‐dihydroxy‐6‐methyl‐4h‐pyran‐4‐one. The study highlighted that heating RT at approximately 300°C could mitigate the production of harmful substances while still providing a familiar sensory experience with combusted tobacco.

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Nicotine-like behavioral effects of the minor tobacco alkaloids nornicotine, anabasine, and anatabine in male rodents.

Cited by 57 publications

References 55 publications

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

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

Determination of Behaviorally Effective Tobacco Constituent Doses in Rats

Multiple analyses of main flavor components in reconstituted tobacco and transfer behavior of their key substances during heating

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