Nicotinic effects of tobacco smoke constituents in nonhuman primates

Desai, Rajeev I.; Doyle, Michelle R.; Withey, Sarah L.; Bergman, Jack

doi:10.1007/s00213-016-4238-5

Cited by 10 publications

(16 citation statements)

References 37 publications

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“…(1)-Epibatidine Discrimination Consistent with our previous observations (Desai and Bergman, 2015;Desai et al, 2016a), reliable discriminativestimulus control by 0.001 mg/kg (1)-epibatidine was maintained in all four subjects throughout the present study (Fig. 3, top panel).…”

Section: Food-reinforced Behaviorsupporting

confidence: 91%

“…The nAChR partial agonist, lobeline, did not generalize for (1)-epibatidine (8% 6 5%). The effects of higher doses of each of these nicotinic partial agonists were not determined because in the present or previous studies 0.25 or 0.5 log-unit higher doses either markedly disrupted responding or produced untoward effects in squirrel monkeys (Desai and Bergman, 2014;Desai et al, 2016a). Based on the mean ED 50 values, the rank order of potency of drugs that produced epibatidine-like effects was (1)-epibatidine (2)-epibatidine .…”

Section: Food-reinforced Behaviormentioning

confidence: 87%

“…The discrimination training procedure used to establish (1)-epibatidine discrimination has been described previously (Desai and Bergman, 2015;Desai et al, 2016a). Briefly, seated subjects were trained to turn off stimulus lights under a 10-response FR, 50-second TO schedule of stimulus termination.…”

Section: Food-reinforced Behaviormentioning

confidence: 99%

“…Next, we employed drug discrimination methodology in a separate group of squirrel monkeys to determine whether agonists that varied in efficacy and selectivity at nAChR subtypes and non-nicotinic drugs [methamphetamine (MA; indirect monoaminergic agonist), citalopram (serotonin reuptake inhibitor), atropine (muscarinic antagonist), and arecoline (muscarinic agonist)] substituted for the nicotinic agonist (1)-epibatidine. We used (1)-epibatidine discrimination because previous research suggests that its behavioral actions, like those of nicotine, are mediated primarily through a4b2 nAChR mechanisms, (e.g., Dukat and Glennon, 2003;Desai et al, 2016a). The nicotinic drugs studied included a4b2 nAChR subtype-selective ligands previously characterized as either full agonists [nicotine, (2)-epibatidine, and (1)-epibatidine] or partial agonists (isoarecolone, varenicline, cytisine, and lobeline) (Anderson and Arneric, 1994;Badio and Daly, 1994;Hahn et al, 2003;Rollema et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Involvement of Nicotinic Receptor Subtypes in the Behavioral Effects of Nicotinic Drugs in Squirrel Monkeys

Withey

Doyle

Bergman

et al. 2018

J Pharmacol Exp Ther

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Evidence suggests that the 42, but not the 7, subtype of the nicotinic acetylcholine receptor (nAChR) plays a key role in mediating the behavioral effects of nicotine and related drugs. However, the importance of other nAChR subtypes remains unclear. The present studies were conducted to examine the involvement of nAChR subtypes by determining the effects of selected nicotinic agonists and antagonists in squirrel monkeys either 1) responding for food reinforcement or 2) discriminating the nicotinic agonist (+)-epibatidine (0.001 mg/kg) from vehicle. In food-reinforcement studies, nicotine, (+)-epibatidine, varenicline and cytisine all produced dose-dependent decreases in rates of food-maintained responding. The rate-decreasing effects of nicotine were antagonized by mecamylamine (nonselective), not appreciably altered by dihydro--erythroidine (42 selective), and exacerbated by the nicotinic partial agonists, varenicline and cytisine. Results from discrimination studies show that non-nicotinic drugs did not substitute for (+)-epibatidine, and that except for lobeline, the nicotinic agonists produced either full [(+)-epibatidine, (-)-epibatidine, and nicotine] or partial (varenicline, cytisine, anabaseine, and isoarecolone) substitution for (+)-epibatidine. In interaction studies with antagonists differing in selectivity, (+)-epibatidine discrimination was substantively antagonized by mecamylamine, slightly attenuated by hexamethonium (peripherally restricted) or dihydro--erythroidine, and not altered by methyllycaconitine (7 selective). Varenicline and cytisine enhanced (+)-epibatidine's discriminative-stimulus effects. Correlational analysis revealed a close correspondence between relative behavioral potencies of nicotinic agonists in both studies and their published relative binding affinities at 42 and 34, but not 7 nAChR, subtypes. Collectively, these results are consistent with the idea that the42 and 34, but not 7 nAChR subtypes play a role in the behavioral effects of nicotinic agonists.

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Section: Food-reinforced Behaviorsupporting

confidence: 91%

Section: Food-reinforced Behaviormentioning

confidence: 87%

Section: Food-reinforced Behaviormentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Involvement of Nicotinic Receptor Subtypes in the Behavioral Effects of Nicotinic Drugs in Squirrel Monkeys

Withey

Doyle

Bergman

et al. 2018

J Pharmacol Exp Ther

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“…Racemic anatabine was marketed as an herbal supplement called Anatabloc by Rock Creek Pharmaceuticals. Several studies supported by this company have shown that anatabine, in addition to its anti-inflammatory actions, has procognitive [40][41][42][43], neuro-protective [44], immune disease modulating [45,46], and smoking cessation actions. Anatabine partially substitutes for nicotine in drug discrimination behavioral assays but does not have the addictive potency of nicotine [47,48].…”

Section: Discussionmentioning

confidence: 99%

A Pharmacological Comparison of Two Isomeric Nicotinic Receptor Agonists: The Marine Toxin Isoanatabine and the Tobacco Alkaloid Anatabine

et al. 2020

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Many organisms possess "secondary" compounds to avoid consumption or to immobilize prey. While the most abundant or active compounds are initially investigated, more extensive analyses reveal other "minor" compounds with distinctive properties that may also be of biomedical and pharmaceutical significance. Here, we present an initial in vitro investigation of the actions of two isomeric tetrahydropyridyl ring-containing anabasine analogs: isoanatabine, an alkaloid isolated from a marine worm, and anatabine, a relatively abundant minor alkaloid in commercial tobacco plants. Both compounds have a double bond that is distal to the piperidine ring nitrogen of anabasine. Racemic isoanatabine and anatabine were synthesized and their S-and R-enantiomers were isolated by chiral high pressure liquid chromatography (HPLC). Both isoanatabines displayed higher efficacies at α4β2 nicotinic acetylcholine receptors (nAChRs) relative to the anatabines; R-isoanatabine was most potent. Radioligand binding experiments revealed similar α4β2 nAChR binding affinities for the isoanatabines, but R-anatabine affinity was twice that of S-anatabine. While the two anatabines and S-isoanatabine were highly efficacious agonists at α7 nAChRs, R-isoanatabine was only a weak partial agonist. The four compounds share an ability to stimulate both α4β2 and α7 nAChRs, a property that may be useful in developing more efficacious drugs to treat neurodegenerative and other medical disorders.

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Effects of nicotine-containing and “nicotine-free” e-cigarette refill liquids on intracranial self-stimulation in rats

Harris

Muelken

Smethells

et al. 2018

Drug and Alcohol Dependence

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Nicotinic effects of tobacco smoke constituents in nonhuman primates

Abstract: Selected minor tobacco alkaloids have nicotinic-like effects that may contribute to tobacco consumption and addiction.

Cited by 10 publications

References 37 publications

Involvement of Nicotinic Receptor Subtypes in the Behavioral Effects of Nicotinic Drugs in Squirrel Monkeys

Involvement of Nicotinic Receptor Subtypes in the Behavioral Effects of Nicotinic Drugs in Squirrel Monkeys

A Pharmacological Comparison of Two Isomeric Nicotinic Receptor Agonists: The Marine Toxin Isoanatabine and the Tobacco Alkaloid Anatabine

Effects of nicotine-containing and “nicotine-free” e-cigarette refill liquids on intracranial self-stimulation in rats

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