The influence of mecamylamine on ethanol and sucrose self-administration

Ford, Matthew M.; Fretwell, Andrea M.; Nickel, Jeffrey D.; Mark, Gregory P.; Strong, Moriah N.; Yoneyama, Naomi; Finn, Deborah A.

doi:10.1016/j.neuropharm.2009.05.012

Cited by 35 publications

(36 citation statements)

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“…These results may support role of CB1 activity in the consumption of hedonically rewarding substances [50, 51]. These effects appear to be receptor-specific as mecamylamine, a nicotinic receptor antagonist, reduces ethanol drinking bout frequency but not intrabout composition [36], and raclopride, a dopamine D2 receptor antagonist, decreases total ethanol intake via a specific reduction in number of lick runs [38]. All together, these data strongly support the idea that specific pharmacological interventions can be aimed at reducing ethanol intake through a number of distinct mechanisms.…”

Section: Discussionmentioning

confidence: 61%

Microstructural analysis of rat ethanol and water drinking patterns using a modified operant self-administration model

Robinson

McCool

2015

Physiology & Behavior

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Background Ethanol drinking pattern has emerged as an important factor in the development, maintenance, and health consequences of alcohol use disorders in humans. The goal of these studies was to further our understanding of this important factor through refinement of an operant rodent model of ethanol consumption capable of drinking pattern microstructural analysis. We evaluated measures of total consumption, appetitive behavior, and drinking microstructure for ethanol and water at baseline and assessed alterations induced by two treatments previously shown to significantly alter gross ethanol appetitive and consummatory behaviors in opposing directions. Methods Male Long Evans rats were trained on an FR1 operant paradigm which allowed for continuous liquid access until an 8 second pause in consumption resulted in termination of liquid access. Total appetitive and consummatory behaviors were assessed in addition to microstructural drinking pattern for both ethanol and water during a five day baseline drinking period, after chronic intermittent ethanol vapor exposure, and following administration of a cannabinoid receptor antagonist SR141716a. Results As in previous operant studies, ethanol vapor exposure resulted in increases in ethanol-directed responding, total consumption, and rate of intake. Further, striking differential alterations to ethanol and water bout size, duration, and lick pattern occurred consistent with alterations in hedonic evaluation. Vapor additionally specifically reduced the number of ethanol-directed lever presses which did not result in subsequent consumption. SR141716a administration reversed many of these effects. Conclusions The addition of microstructural analysis to operant self-administration by rodents provides a powerful and translational tool for the detection of specific alterations in ethanol drinking pattern which may enable insights into neural mechanisms underlying specific components of drug consumption.

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Section: Discussionmentioning

confidence: 61%

Microstructural analysis of rat ethanol and water drinking patterns using a modified operant self-administration model

Robinson

McCool

2015

Physiology & Behavior

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“…Our finding is supported by a recent study which found that mecamylamine decreased pavlovian incentive motivation for sugar (Ostlund et al, 2014) and operant self-administration, albeit at much higher doses (Ford et al, 2009). Further, an in vitro application of mecamylamine in the NAc, decreased ghrelin-mediated accumbal DA release (Palotai et al, 2013).…”

Section: Discussionsupporting

confidence: 88%

“…Interestingly, a recent study found that pavlovian incentive motivation for sugar was disrupted with systemic mecamylamine administration (Ostlund et al, 2014). Also, systemic mecamylamine was also shown to reduce sucrose self-administration, albeit at much higher doses (Ford et al, 2009).…”

Section: Chapter 5: General Discussionmentioning

confidence: 99%

The Effects of Binge-Like Sucrose Consumption on the Mesolimbic Reward Pathway in the Brain

Shariff¹

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Obesity is becoming a worldwide epidemic (WHO, 2000, Leigh and Morris, 2016, Lifshitz and Lifshitz, 2014, James, 2004. Pharmacotherapeutics that attempt to stem overweight and obesity have largely been ineffective and often are accompanied by adverse side effects (Glazer, 2001). It is therefore imperative to develop effective strategies to combat obesity. A paradigm that has gained momentum relatively recently is the development of addiction to fat and sweet food (Fortuna, 2012, Smith and Robbins, 2013, Volkow et al., 2013a. While drugs of abuse affect various brain subregions, they have been shown to act on three major areas of the brain, namely the brain stem, the limbic system and the cerebral cortex (NIDA, 2010).The limbic system is an interconnected collection of brain structures such as the nucleus accumbens (NAc) and the basolateral amygdala (BLA), whose neural connectivities encode emotional states such as anticipation of reward and motivation (Berridge, 2012). At the molecular level, in addition to the various dysregulatory outcomes in relation to neurotransmitters, it is the dysregulation of balance between dopamine (DA) and acetylcholine (ACh) in the limbic system, especially in the NAc that has been found to drive and maintain behaviours that perpetuate addiction to substances of abuse (Hoebel et al., 2007, Aosaki et al., 2010. Interestingly, sucrose, a potent contributor to the development of obesity (Lakhan and Kirchgessner, 2013, Tappy et al., 2010), has been shown, albeit indirectly, to affect the release of DA in the NAc via the nAChRs (Avena et al., 2008). The role of specific subtypes of nAChRs in the NAc has yet to be elucidated in relation to sucrose consumption.Firstly, this study establishes that the nAChRs are involved in regulating sucrose consumption. Based on the various nAChRs agonists/partial agonists and antagonists tested systemically, it is surmised that *nAChRs are involved in mediating sucrose consumption.Furthermore, coupled to the changes in nAChRs, this study also sheds light for the first time ii on the global morphological changes that occur in the dendrites of the neurons in the NAc and BLA reminiscent of similar changes due to drugs of abuse, suggestive of a global imbalance at the level of the NAc and amygdala. Further studies are warranted to determine the precise functional significance of the morphological changes that are reported in this study, and to discover potential newer pharmacotherapies that target the nAChRs. At the present time, however, varenicline, an FDA approved pharmacotherapeutic, appears to be an attractive agent in reducing sucrose intake. Varenicline may hold potential benefits in lowering weight gain thus concomitantly lowering the global burden of obesity-related disease.iii

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“…Several electrophysiological and behavioral studies have shown an interaction between pentameric neuronal nicotinic acetylcholine receptors (nAChRs) and ethanol (Narahashi et al, 1999;Larsson and Engel, 2004;Ford et al, 2009). Reports have also shown high-to-moderate densities of nACh receptors in mesolimbic dopamineinnervated areas (Clarke et al, 1984;Klink et al, 2001;Wonnacott et al, 2005;Champtiaux et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory influence of mecamylamine on ethanol withdrawal-induced symptoms in C57BL/6J mice

Bhutada¹,

Mundhada²,

Bansod³

et al. 2010

Behavioural Pharmacology

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Several reports show the involvement of neuronal nicotinic acetylcholine receptors (nAChRs) in the behavioral effects of ethanol, including ethanol drinking and relapse. Therefore, this study evaluated the effects of mecamylamine, a nAChR antagonist, on ethanol withdrawal signs. Ethanol dependence was induced in C57BL/6J mice by ethanol liquid diet administration. Animals were provided with nutritionally balanced control liquid diet (600 kcal/l) as their sole nutrient source on day 0; from days 1 to 4, 3% v/v of ethanol, followed by 6% v/v of ethanol (from days 5 to 7), and 10% v/v of ethanol (from days 8 to 10) were incorporated into the liquid diet. On day 11, ethanol liquid diet was replaced with nutritionally balanced control liquid diet, and ethanol withdrawal-induced physical signs were recorded. Results showed that acute administration of mecamylamine (1-4 mg/kg, intraperitoneally) dose-dependently attenuated ethanol withdrawal-induced signs, and these effects were comparable with those of diazepam (1-2 mg/kg, intraperitoneally). In addition, chronic administration of mecamylamine into ethanol diet-fed mice markedly attenuated the ethanol withdrawal sign scores, thus supporting the contention that nAChR is involved in ethanol dependence. In conclusion, our results suggest that mecamylamine exhibited inhibitory effects on ethanol withdrawal signs which could be mediated through nAChR.

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The influence of mecamylamine on ethanol and sucrose self-administration

Cited by 35 publications

References 50 publications

Microstructural analysis of rat ethanol and water drinking patterns using a modified operant self-administration model

Microstructural analysis of rat ethanol and water drinking patterns using a modified operant self-administration model

The Effects of Binge-Like Sucrose Consumption on the Mesolimbic Reward Pathway in the Brain

Inhibitory influence of mecamylamine on ethanol withdrawal-induced symptoms in C57BL/6J mice

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