A role for neuronal nicotinic acetylcholine receptors in ethanol-induced stimulation, but not cocaine- or methamphetamine-induced stimulation

Kamens, Helen M.; Phillips, Tamara J.

doi:10.1007/s00213-007-0969-7

Cited by 40 publications

(49 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data indicate that there is a requirement for wild-type ACh availability for EHC and are consistent with the hypothesis that ethanol potentiates normal ACh signaling to generate EHC. Consistent with our mecamylamine result, it has been shown that mecamylamine can inhibit the locomotorstimulation effects of ethanol in mice (Kamens and Phillips 2008). Our data indicate that unc-63, which encodes a nAChR a-subunit, is necessary for wild-type levels of EHC ( Figure 3A).…”

Section: Cholinergic Signalingsupporting

confidence: 91%

“…Locomotor activation by low to moderate concentrations of ethanol in rodents is thought to model the euphoric effects of ethanol in humans (Phillips and Shen 1996). Locomotor activation by ethanol has been linked to increased dopamine release in neural reward pathways, possibly via mechanisms that involve inhibition of the inhibitory GA-BA B metabotropic receptors by ethanol (Holstein et al 2009;Kruse et al 2012) and/or by ethanol activation of neuronal nAChRs (Soderpalm et al 2000;Larsson et al 2002;Kamens and Phillips 2008;Kamens et al 2009). Individual variation that alters the mechanisms responsible for the acute behavioral effects of ethanol is likely to contribute to variation in predisposition to develop alcohol use disorders (AUDs).…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Novel Cholinergic Action of Alcohol and the Development of Tolerance to That Effect inCaenorhabditis elegans

et al. 2014

View full text Add to dashboard Cite

Understanding the genes and mechanisms involved in acute alcohol responses has the potential to allow us to predict an individual's predisposition to developing an alcohol use disorder. To better understand the molecular pathways involved in the activating effects of alcohol and the acute functional tolerance that can develop to such effects, we characterized a novel ethanolinduced hypercontraction response displayed by Caenorhabditis elegans. We compared body size of animals prior to and during ethanol treatment and showed that acute exposure to ethanol produced a concentration-dependent decrease in size followed by recovery to their untreated size by 40 min despite continuous treatment. An increase in cholinergic signaling, leading to muscle hypercontraction, is implicated in this effect because pretreatment with mecamylamine, a nicotinic acetylcholine receptor (nAChR) antagonist, blocked ethanol-induced hypercontraction, as did mutations causing defects in cholinergic signaling (cha-1 and unc-17). Analysis of mutations affecting specific subunits of nAChRs excluded a role for the ACR-2R, the ACR-16R, and the levamisole-sensitive AChR and indicated that this excitation effect is dependent on an uncharacterized nAChR that contains the UNC-63 a-subunit. We performed a forward genetic screen and identified eg200, a mutation that affects a conserved glycine in EAT-6, the a-subunit of the Na + /K + ATPase. The eat-6(eg200) mutant fails to develop tolerance to ethanol-induced hypercontraction and remains contracted for at least 3 hr of continuous ethanol exposure. These data suggest that cholinergic signaling through a specific a-subunit-containing nAChR is involved in ethanol-induced excitation and that tolerance to this ethanol effect is modulated by Na + /K + ATPase function.T HE abuse of alcohol is a cause of significant societal and health-related problems. Despite the common usage of this drug, the molecular underpinnings of alcohol's acute actions on the brain are poorly understood. Alcohol (ethanol) has biphasic behavioral effects in humans and other animals, acting as a stimulant at lower concentrations and as a depressant at higher concentrations. Understanding the molecular nature of these biphasic effects is made difficult by the fact that ethanol interacts with, and alters the function of, many proteins, including neurotransmitter receptors and ion channels (Harris et al. 2008;Spanagel 2009). A commonly suggested class of ethanol targets is ligand-gated ion channels (LGICs), which include NMDA glutamate receptors, and members of a subclass of LGICs, the Cys-loop superfamily, including GABA A , glycine, and nicotinic acetylcholine receptors (nAChRs) (Olsen et al. 2014). Effects on the GABA A and glutamate receptors are hypothesized to play a significant role in the depressant effects of ethanol (Harris et al. 2008). Locomotor activation by low to moderate concentrations of ethanol in rodents is thought to model the euphoric effects of ethanol in humans (Phillips and Shen 1996). Locomotor activat...

show abstract

Section: Cholinergic Signalingsupporting

confidence: 91%

mentioning

confidence: 99%

A Novel Cholinergic Action of Alcohol and the Development of Tolerance to That Effect inCaenorhabditis elegans

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Moreover, there are several in vivo studies supporting the idea that ␣4␤2* (Owens et al, 2003;Butt et al, 2004) and ␣7* (Wehner et al, 2004) nAChR are modulated by ethanol, whereas other pharmacological studies in experimental animals seem to exclude the involvement of these nAChR subtypes in several important aspects of alcohol reinforcement. In rodents, the ␣4␤2* nAChR antagonist dihydro-␤-erythroidine does not affect alcohol consumption (Lê et al, 2000), ethanol-induced locomotor activity (Larsson et al, 2002;Kamens and Phillips, 2008), dopamine overflow (Larsson et al, 2002;Ericson et al, 2003), or conditioned reinforcement to ethanol (Löf et al, 2007). Moreover, the ␣7* nAChRs antagonist methyllycaconitine citrate had no effect on ethanol-induced dopamine elevations or locomotor activity in rodents (Larsson et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

The Smoking Cessation Medication Varenicline Attenuates Alcohol and Nicotine Interactions in the Rat Mesolimbic Dopamine System

Ericson

Löf

Stomberg³

et al. 2009

J Pharmacol Exp Ther

107

View full text Add to dashboard Cite

Varenicline was recently approved as an aid for smoking cessation. Patients treated with varenicline have reported a concomitant reduction in their alcohol consumption. This compound has also been demonstrated to reduce alcohol seeking and consumption in alcohol high-preferring rats. Based on the extensive coabuse of nicotine and alcohol, the aim of the present study was to explore whether interactions among varenicline, nicotine, and ethanol in the brain reward system could indicate the use of varenicline also for alcohol dependence. Using the in vivo microdialysis method, we investigated the effects of systemic injections of varenicline on the extracellular accumbal dopamine levels in response to a systemic challenge of ethanol, nicotine, or the combination of nicotine and ethanol in the experimental rat. Acute systemic coadministration of varenicline and ethanol counteracted each others' respective enhancing effect on dopamine levels in the nucleus accumbens. However, after 5 days of varenicline pretreatment, acute combined varenicline and ethanol administration raised dopamine levels to the same extent as either drug alone. Furthermore, after varenicline pretreatment an acute injection of varenicline antagonized the dopamine stimulatory effect of acute nicotine as well as that of systemic coadministration of ethanol and nicotine. In contrast, a pronounced additive dopamine increase was observed when nicotine and ethanol were coadministered in vehicle-pretreated rats. The antismoking agent varenicline exhibits properties with respect to its interaction with ethanol and nicotine in the brain reward system that may be beneficial for treating patients with alcohol dependence with (and possibly also without) concomitant nicotine dependence.

show abstract

“…injections of mecamylamine a comparatively low dose of 3 μg was used since higher doses have been reported to have unspecific effects, for example, on the NMDA receptor (O'Dell andChristensen, 1988, Papke et al, 2001). Hexamethonium (Sigma-Aldrich, Munich, Germany) was dissolved in normal saline and administered at 2 mg/kg i.p, in a volume of 1 mL/kg, a dose used previously in comparative studies with mecamylamine of central and peripheral effects of nAChR signaling (Tani et al, 1997, Kamens andPhillips, 2008). All central injections were performed using a microinfusion pump (CMA 400 syringe pump, Solna, Sweden).…”

Section: Methodsmentioning

confidence: 99%

Blockade of central nicotine acetylcholine receptor signaling attenuate ghrelin-induced food intake in rodents

et al. 2010

View full text Add to dashboard Cite

A role for neuronal nicotinic acetylcholine receptors in ethanol-induced stimulation, but not cocaine- or methamphetamine-induced stimulation

Abstract: Neuronal nicotinic receptors are involved in EtOH, but not psychostimulant, stimulation. These studies suggest a lack of involvement of some nicotinic receptor subtypes, but more work is needed to determine the specific receptor subtypes involved in this behavior.

Cited by 40 publications

References 57 publications

A Novel Cholinergic Action of Alcohol and the Development of Tolerance to That Effect inCaenorhabditis elegans

A Novel Cholinergic Action of Alcohol and the Development of Tolerance to That Effect inCaenorhabditis elegans

The Smoking Cessation Medication Varenicline Attenuates Alcohol and Nicotine Interactions in the Rat Mesolimbic Dopamine System

Blockade of central nicotine acetylcholine receptor signaling attenuate ghrelin-induced food intake in rodents

Contact Info

Product

Resources

About