Effects of nornicotine enantiomers on intravenous S(−)-nicotine self-administration and cardiovascular function in rats

Stairs, Dustin J.; Neugebauer, Nicole; Wei, Xiangdong; Boustany, Carine; Hojahmat, Marhaba; Cassis, Lisa A.; Crooks, Peter A.; Dwoskin, Linda P.; Bardo, Michael T.

doi:10.1007/s00213-006-0610-1

Cited by 13 publications

(14 citation statements)

References 30 publications

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“…As stated previously, biphasic patterns on nicotine intake have been observed with bupropion depending on the dose administered, and there is much speculation regarding the mechanism behind these differential effects. However, it has been suggested that bupropion's effects on nicotine addiction lie outside the primary or conditioned reinforcing effects of nicotine (Liu et al , 2008, Paterson et al , 2007, Paterson et al , 2008, Stairs et al , 2007). …”

Section: Discussionmentioning

confidence: 99%

Bupropion–varenicline interactions and nicotine self-administration behavior in rats

Hall¹,

Slade²,

Wells³

et al. 2015

Pharmacology Biochemistry and Behavior

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Varenicline and bupropion each have been shown to significantly improve cessation of tobacco addiction in humans. They act through different mechanisms and the question about the potential added efficacy with their combined used has arisen. Preclinical animal models of nicotine addiction can help with the evaluation of this combined approach and what dose combinations of varenicline and bupropion may be useful for enhancing tobacco cessation. In this study, we investigated the interacting dose-effect functions of varenicline and bupropion in a rat model of nicotine self-administration. Young adult female Sprague-Dawley rats were allowed to self-administer nicotine in one-hr sessions under an FR1 reinforcement schedule. Varenicline (0.3, 1. 3 mg/kg) and bupropion (8.33, 25, 75 mg/kg) were administered alone or together 15 min before each session. The vehicle saline was the control. Higher doses of each drug alone reduced nicotine self-administration compared to control with reductions of 62% and 75% with 3 mg/kg varenicline and 75 mg/kg bupropion respectively. Lower dose varenicline which does not by itself reduce nicotine self-administration, significantly augmented bupropion effects. The 0.3 mg/kg varenicline dose combined with the 25 and 75 mg/kg bupropion doses caused greater reductions of nicotine self-administration than either dose of bupropion given alone. However, higher dose varenicline did not have this effect. Lower dose bupropion did not augment varenicline effects. Only the high bupropion dose significantly enhanced the varenicline effect. Likewise, combinding 1 mg/kg varenicline with 75 mg/kg bupropion reduced self-administration to a greater extent than either dose alone. These results demonstrate that combination therapy with varenicline and bupropion may be more beneficial than monotherapy with either drug alone.

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Section: Discussionmentioning

confidence: 99%

Bupropion–varenicline interactions and nicotine self-administration behavior in rats

Hall¹,

Slade²,

Wells³

et al. 2015

Pharmacology Biochemistry and Behavior

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“…Stable responding was defined as three consecutive sessions with less than 25% variation in the total number of responses during the cocaine components and at least a 2:1 ratio in the number of responses on the cocaine lever compared to the sucrose lever during the cocaine components. Using these criterion, which our laboratory have use previously with a simple FR schedule (Stairs et al, 2007), 12 animals acquired stable cocaine self-administration after 12–14 sessions; 3 other rats did not reach criteria and 3 had a catheter malfunction that prevented inclusion of the data. Once responding stabilized, varying doses of SCH 23390 (0, 2.5, 5, and 10 µg/kg, s.c.) were administered in a latin square design 25 min prior to the session.…”

Section: Methodsmentioning

confidence: 99%

Nicotine and cocaine self-administration using a multiple schedule of intravenous drug and sucrose reinforcement in rats

Stairs

Neugebauer

Bardo

2010

Behavioural Pharmacology

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There appears to be a relatively narrow range of contingencies in which intravenous (i.v) infusions of nicotine will maintain responding in rats. The schedule of reinforcement typically used when investigating i.v. nicotine self-administration is a simple fixed-ratio (FR) schedule. The current study determined if responding in rats could be established using a multiple (Mult) schedule of either i.v. cocaine or nicotine and sucrose reinforcement. Following training of individual components with each reinforcer, rats were placed on an FR15 60-sec timeout Mult schedule of cocaine (0.3 mg/kg/infusion) and sucrose (45 mg pellets) reinforcement or an FR5 60-sec timeout Mult schedule of nicotine (0.03 mg/kg/infusion) and sucrose (45 mg pellets) reinforcement. Both cocaine and nicotine maintained significant levels of responding under the Mult schedule. Pretreatment with the dopamine D1 antagonist SCH 23390 increased cocaine-maintained responding, but not sucrose responding. Acute pretreatment with the nicotinic antagonist mecamylamine or SCH 23390 specifically decreased nicotine self-administration. Extinction of the individual nicotine and sucrose components resulted in decreases in responding in each component under extinction. These results indicate that i.v. nicotine maintains responding under a Mult schedule. This procedure may be useful when studying the specificity of drug pretreatments on nicotine self-administration.

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“…Nornicotine has been shown to support self-administration by itself, but higher doses are required and lower response rates are attained (Bardo et al, 1999). Conversely, large doses of nornicotine administered to rats prior to a nicotine self-administration session also inhibited nicotine self-administration (Green et al, 2000;Stairs et al, 2007). Additional studies not utilizing self-administration also suggest that the minor alkaloids may have actions relevant to reward (Dwoskin et al, 1995;Green, Brown, Phillips, Dwoskin, & Bardo, 2002;Papke, Dwoskin, & Crooks, 2007).…”

Section: Could Other Constituents Of Tobacco Impact the Threshold Formentioning

confidence: 99%

Impact of Tobacco Regulation on Animal Research: New Perspectives and Opportunities

Donny

Taylor

LeSage

et al. 2012

Nicotine & Tobacco Research

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Introduction: The Family Smoking Prevention and Tobacco Control Act in the United States and the World Health Organization Framework Convention on Tobacco or Health ratified by over 170 countries render scientific investigations into the abuse liability, harm, and effects of tobacco more critical than ever. A key area to explore relates to the potential regulation of nicotine content in cigarettes. Determining the nicotine content per cigarette below which smokers reliably reduce their consumption of and dependence on cigarettes, an idea proposed almost 20 years ago (Benowitz & Henningfield, 1994), could be a powerful approach to reduce the abuse liability and consequent harm from cigarettes. However, this approach is laden with potentially complex issues. Many of these complications can be studied using animal models, but they require a particular perspective.

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Effects of nornicotine enantiomers on intravenous S(−)-nicotine self-administration and cardiovascular function in rats

Abstract: Both R(+)- and S(-)-nornicotine may have potential utility as a novel tobacco use cessation agent.

Cited by 13 publications

References 30 publications

Bupropion–varenicline interactions and nicotine self-administration behavior in rats

Bupropion–varenicline interactions and nicotine self-administration behavior in rats

Nicotine and cocaine self-administration using a multiple schedule of intravenous drug and sucrose reinforcement in rats

Impact of Tobacco Regulation on Animal Research: New Perspectives and Opportunities

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