Electrophysiological characterization of harmane-induced activation of mesolimbic dopamine neurons

Arib, Ouafa; Rat, Pascal; Molimard, R; Chait, Abderrahman; Fauré, Philippe; Beaurepaire, Renaud de

doi:10.1016/j.ejphar.2009.12.012

Cited by 31 publications

(25 citation statements)

References 28 publications

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“…The two compounds may also be formed in cigarette smoke or in vivo by chemical reactions between indolamines and aldehydes (e.g., acetaldehyde) that are created by combustion of tobacco (poly)saccharides (Cao et al , 2007). Like the minor alkaloids discussed above, both compounds elicit dopamine efflux in mesolimbic dopamine neurons, in what has been described as a dose-dependent, U-shaped manner (Arib et al , 2010, Baum et al , 1996). However, with regard to tobacco use, harmane and norharmane have received much more attention for their ability to inhibit both isoforms of monoamine oxidase (MAO).…”

Section: Introductionmentioning

confidence: 93%

Differential effects of non-nicotine tobacco constituent compounds on nicotine self-administration in rats

Hall

Wells

Allenby

et al. 2014

Pharmacology Biochemistry and Behavior

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Tobacco smoking has been shown to be quite addictive in people. However, nicotine itself is a weak reinforcer compared to other commonly abused drugs, leading speculation that other factors contribute to the high prevalence of tobacco addiction in the human population. In addition to nicotine, there are over 5000 chemical compounds that have been identified in tobacco smoke, and more work is needed to ascertain their potential contributions to tobacco’s highly addictive properties, or as potential candidates for smoking cessation treatment. In this study, we examined seven non-nicotine tobacco constituent compounds (anabasine, anatabine, nornicotine, myosmine, harmane, norharmane, and tyramine) for their effects on nicotine self-administration behavior in rats. Young adult female Sprague-Dawley rats were allowed to self-administer nicotine (0.03 mg/kg/ 50 μl infusion) under a fixed ratio-1 schedule of reinforcement. Each self-administration session lasted 45 min. Doses of each tobacco constituent compound were administered subcutaneously 10 min prior to the start of each session in a repeated measures, counterbalanced order two times. Anabasine displayed a biphasic dose-effect function. Pretreatment with 0.02 mg/kg anabasine resulted in a 25% increase in nicotine self-administration, while 2.0 mg/kg of anabasine reduced nicotine infusions per session by over 50%. Pretreatment with 2.0 mg/kg anatabine also significantly reduced nicotine self-administration by nearly half. These results suggest that some non-nicotine tobacco constituents may enhance or reduce nicotine’s reinforcing properties. Also, depending upon the appropriate dose, some of these compounds may also serve as potential smoking cessation agents.

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Section: Introductionmentioning

confidence: 93%

Differential effects of non-nicotine tobacco constituent compounds on nicotine self-administration in rats

Hall

Wells

Allenby

et al. 2014

Pharmacology Biochemistry and Behavior

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“…These compounds are MAO inhibitors (Herraiz, 2004) and may contribute to the MAO inhibition observed in smokers at the concentrations present in cigarette smoke (Rommelspacher, Meier-Henco, Smolka, & Kloft, 2002). However, they also appear to have actions independent of MAO inhibition (Arib et al, 2010;Rommelspacher et al, 2002;Touiki, Rat, Molimard, Chait, & de Beaurepaire, 2005). Large doses of norharman enhance responding for nicotine in rats on a progressive ratio, but not an FR, schedule of reinforcement (Guillem et al, 2006).…”

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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“…This alkaloid has also been shown to act on various receptor systems in the brain (Zetler et al 1972), such as serotonin, opiate, dopamine, imidazoline and benzodiazepines (Squires et al 2004;Nasehi et al 2010). Harmane is a potent inhibitor of monoamine oxidase, particularly subtype A (Anderson et al 2003;Arib et al 2010). Furthermore, harmane exerts strong inhibition against acetylcholinesterase and butyrylcholinesterase (Zhao et al 2013).…”

Section: Harmanementioning

confidence: 99%

Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS

Liu

et al. 2016

Pharmaceutical Biology

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Context The b-carboline alkaloid harmane is widely distributed in common foods, beverages and hallucinogenic plants. Harmane exerts potential in therapies for Alzheimer's and depression diseases. However, little information on its dynamic metabolic profiles and pharmacokinetics in vivo is currently available. Objective This study investigates the dynamic metabolic profiles and pharmacokinetic properties of harmane and its metabolites in rats in vivo. Materials and methods A highly selective, sensitive and rapid ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and well-validated for simultaneous quantitative determination of harmane and its uncertain endogenous metabolite harmine, as well as for semiquantitative determination of 10 harmane metabolites in rats after intravenous injection and oral administration of harmane at 1.0 and 30.0 mg/kg, respectively. Results The calibration curves of harmane and harmine showed excellent linearity within the concentration range of 1-2000 ng/mL with acceptable accuracy, precision, selectivity, recovery, matrix effect and stability. Ten metabolites, including harmane but not harmine, were detected and identified after intravenous and oral administration of harmane. The absolute bioavailability of harmane following an oral dose was 19.41 ± 3.97%. According to the AUC 0-t values of all the metabolites, the metabolic levels of phase II metabolites were higher than those of phase I metabolites, and the sulphation pathways were the dominant metabolic routes for harmane in both routes of administration. Discussion and conclusion The pharmacokinetic properties of harmane and its 10 metabolites in rats were determined. Sulphate conjugation was the predominant metabolic process of harmane in rats.

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Electrophysiological characterization of harmane-induced activation of mesolimbic dopamine neurons

Cited by 31 publications

References 28 publications

Differential effects of non-nicotine tobacco constituent compounds on nicotine self-administration in rats

Differential effects of non-nicotine tobacco constituent compounds on nicotine self-administration in rats

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

Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS

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