Oral sazetidine-A, a selective α4β2* nicotinic receptor desensitizing agent, reduces nicotine self-administration in rats.

dc.contributor.author

Rezvani, Amir H

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Wells, Corinne

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Slade, Susan

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Xiao, Yingxian

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Kellar, Kenneth J

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Levin, Edward D

dc.date.accessioned

2023-12-07T00:32:17Z

dc.date.available

2023-12-07T00:32:17Z

dc.date.issued

2019-04

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2023-12-07T00:32:16Z

dc.description.abstract

Sazetidine-A selectively desensitizes α4β2 nicotinic receptors and also has partial agonist effects. We have shown that subcutaneous acute and repeated injections as well as chronic infusions of sazetidine-A significantly reduce intravenous (IV) nicotine self-administration in rats. To further investigate the promise of sazetidine-A as a smoking cessation aid, it is important to determine sazetidine-A effects with oral administration and the time-effect function for its action on nicotine self-administration. Young adult female Sprague-Dawley rats were trained to self-administer IV nicotine at the benchmark dose of 0.03 mg/kg/infusion dose in an operant FR1 schedule in 45-min sessions. After five sessions of training, they were tested for the effects of acute oral doses of sazetidine-A (0, 0.3, 1 and 3 mg/kg) given 30 min before testing. To determine the time-effect function, these rats were administered 0 or 3 mg/kg of sazetidine-A 1, 2, 4 or 23 h before the onset of testing. Our previous study showed that with subcutaneous injections, only 3 mg/kg of sazetidine-A significantly reduced nicotine self-administration, however, with oral administration of sazetidine-A lower dose of 1 mg/kg was also effective in reducing nicotine intake. A similar effect was seen in the time-effect study with 3 mg/kg of oral sazetidine-A causing a significant reduction in nicotine self-administration across all the time points of 1, 2, 4 or 23 h after oral administration. These results advance the development of sazetidine-A as a possible aid for smoking cessation by showing effectiveness with oral administration and persistence of the effect over the course of a day.

dc.identifier

S0091-3057(18)30568-9

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0091-3057

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1873-5177

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https://hdl.handle.net/10161/29513

dc.language

eng

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Elsevier BV

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Pharmacology, biochemistry, and behavior

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10.1016/j.pbb.2019.02.007

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Animals

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Rats

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Rats, Sprague-Dawley

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Nicotine

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Azetidines

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Pyridines

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Receptors, Nicotinic

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Nicotinic Agonists

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Administration, Oral

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Female

dc.title

Oral sazetidine-A, a selective α4β2* nicotinic receptor desensitizing agent, reduces nicotine self-administration in rats.

dc.type

Journal article

duke.contributor.orcid

Levin, Edward D|0000-0001-7292-8084|0000-0002-5060-9602

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109

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112

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Duke

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Nicholas School of the Environment

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School of Medicine

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Trinity College of Arts & Sciences

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Pharmacology & Cancer Biology

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Psychiatry & Behavioral Sciences

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Duke Cancer Institute

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Psychology & Neuroscience

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Environmental Sciences and Policy

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Institute for Brain Sciences

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Initiatives

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Duke Science & Society

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Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences

pubs.publication-status

Published

pubs.volume

179

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