Effects of Combined Systemic Alcohol and Central Nicotine Administration into Ventral Tegmental Area on Dopamine Release in the Nucleus Accumbens

Tizabi, Yousef; Copeland, Robert L.; Louis, Vely A.; Taylor, Robert E.

doi:10.1111/j.1530-0277.2002.tb02551.x

Cited by 160 publications

(63 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…17). ACh levels in the ventral tegmental area are increased in highbut not low-ethanol consuming rats (28), and the nonselective nAChR antagonist mecamylamine decreases ethanol consumption in high-alcohol-preferring rats (20,21) and blocks ethanolinduced dopamine release (21,23,24).…”

Section: Discussionmentioning

confidence: 99%

“…The nAChRs are well characterized ligandgated ion channels that, in addition to mediating the rewarding properties of nicotine, also regulate several central functions, such as memory and attention, sleep and wakefulness, anxiety and pain (19). The nAChRs have received little attention despite evidence that they play a role in the development of alcohol dependence.Studies have shown that the nonselective nAChR antagonist, mecamylamine, decreases ethanol consumption in rats (20)(21)(22) and attenuates ethanol-induced dopamine release in the nucleus accumbens (21,23,24). Furthermore, mecamylamine has been reported to block the stimulant or euphoric subjective effects of alcohol and decreases the self-reported desire to consume more alcohol in healthy human volunteers (25-27).…”

mentioning

confidence: 99%

“…Studies have shown that the nonselective nAChR antagonist, mecamylamine, decreases ethanol consumption in rats (20)(21)(22) and attenuates ethanol-induced dopamine release in the nucleus accumbens (21,23,24). Furthermore, mecamylamine has been reported to block the stimulant or euphoric subjective effects of alcohol and decreases the self-reported desire to consume more alcohol in healthy human volunteers (25-27).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking

Steensland

Simms

Holgate

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

342

370

View full text Add to dashboard Cite

Alcohol dependence is a disease that impacts millions of individuals worldwide. There has been some progress with pharmacotherapy for alcohol-dependent individuals; however, there remains a critical need for the development of novel and additional therapeutic approaches. Alcohol and nicotine are commonly abused together, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Varenicline, a partial agonist at the ␣4␤2 nAChRs, reduces nicotine intake and was recently approved as a smoking cessation aid. We have investigated the role of varenicline in the modulation of ethanol consumption and seeking using three different animal models of drinking. We show that acute administration of varenicline, in doses reported to reduce nicotine reward, selectively reduced ethanol but not sucrose seeking using an operant self-administration drinking paradigm and also decreased voluntary ethanol but not water consumption in animals chronically exposed to ethanol for 2 months before varenicline treatment. Furthermore, chronic varenicline administration decreased ethanol consumption, which did not result in a rebound increase in ethanol intake when the varenicline was no longer administered. The data suggest that the ␣4␤2 nAChRs may play a role in ethanol-seeking behaviors in animals chronically exposed to ethanol. The selectivity of varenicline in decreasing ethanol consumption combined with its reported safety profile and mild side effects in humans suggest that varenicline may prove to be a treatment for alcohol dependence.A lcohol dependence constitutes one of the most serious public health problems worldwide. There are only three medications available for the treatment of alcohol dependence; disulfiram, acamprosate, and naltrexone. The opioid antagonist, naltrexone, has demonstrated the most consistent effect in reducing alcohol consumption in the context of behavioral therapy (1). Naltrexone has been shown to decrease ethanol consumption in numerous animal (2-6) and clinical studies (7-10) and has been shown to be more effective in heavy or excessive drinkers (11). However, not all patients respond to naltrexone, which is partly explained by genetic variations in the opioid receptor gene (12). Furthermore, opioid receptor antagonists decrease both ethanol and sucrose intake in rodents (13,14). Alcohol dependence is a complex disorder that will require the use of different therapeutic approaches to treat the disease effectively.Environmental and genetic factors contribute to an individual's risk of becoming dependent on drugs of abuse such as ethanol and nicotine. Approximately 85% of alcoholics smoke, and it has been suggested that common genes control the development of both alcohol and nicotine dependence (15). Furthermore, heavy drinkers tend to be heavy smokers, and alcohol influences nicotine dependence (16). Both nicotine and ethanol can either directly or indirectly activate the brain reward system through neuronal nicotinic acetylcholine re...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking

Steensland

Simms

Holgate

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

342

370

View full text Add to dashboard Cite

show abstract

“…While the different peptide systems may be involved, the strongest available evidence is provided by studies of the mesolimbic dopaminergic system showing nicotine and ethanol to have both additive and synergistic effects on mesocorticolimbic DA signaling. This has been revealed using systemic administration of nicotine plus accumbal administration of ethanol, which together increase DA levels in the accumbens to a greater extent than administration of either drug alone (Tizabi, Bai, Copeland, & Taylor, 2007; Tizabi, Copeland, Louis, & Taylor, 2002). Nicotine and ethanol are also found to act synergistically when administered directly into the posterior VTA, where the mixture of these two drugs as compared to either alone produces a greater change in gene expression in mesolimbic DA neurons (Truitt et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet

Karatayev

Lukatskaya

Moon

et al. 2015

Alcohol

View full text Add to dashboard Cite

Clinical studies demonstrate frequent co-existence of nicotine and alcohol abuse and suggest that this may result, in part, from the ready access to and intake of fat-rich diets. Whereas animal studies show that high-fat diet intake in adults can enhance the consumption of either nicotine or ethanol and that maternal consumption of a fat-rich diet during pregnancy increases operant responding for nicotine in offspring, little is known about the impact of dietary fat on the co-abuse of these two drugs. The goal of this study was to test in Long-Evans rats the effects of perinatal exposure to fat on the co-use of nicotine and ethanol, using a novel paradigm that involves simultaneous intravenous (IV) self-administration of these two drugs. Fat- vs. chow-exposed offspring were characterized and compared, first in terms of their nicotine self-administration behavior, then in terms of their nicotine/ethanol self-administration behavior, and lastly in terms of their self-administration of ethanol in the absence of nicotine. The results demonstrate that maternal consumption of fat compared to low-fat chow during gestation and lactation significantly stimulates nicotine self-administration during fixed-ratio testing. It also increases nicotine/ethanol self-administration during fixed-ratio and dose-response testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint during progressive ratio testing. Of particular note is the finding that rats perinatally exposed to fat self-administer significantly more of the nicotine/ethanol mixture as compared to nicotine alone, an effect not evident in the chow-control rats. After removal of nicotine from the nicotine/ethanol mixture, this difference between the fat- and chow-exposed rats was lost, with both groups failing to acquire the self-administration of ethanol alone. Together, these findings suggest that perinatal exposure to a fat-rich diet, in addition to stimulating self-administration of nicotine, causes an even greater vulnerability to the excessive co-use of nicotine and ethanol.

show abstract

“…Varenicline, the 4 2 nAChR partial agonist, has been found to decrease alcohol consumption and alcohol-seeking behavior in an animal model [308]. In addition to behavioral assays, neurochemical studies suggest that mecamylamine attenuated ethanolinduced extracellular DA levels in the mesolimbic system of rats and mice [306,[309][310][311][312][313]. Furthermore, pretreatment or intra-VTA perfusion of mecamylamine reduces voluntary alcohol-intake and preference in alcohol preferring rats [310,314].…”

Section: Alcoholismmentioning

confidence: 96%

Neuronal Nicotinic Receptors as Brain Targets for Pharmacotherapy of Drug Addiction

Rahman¹,

López-Hernández²,

Corrigall³

et al. 2008

CNSNDDT

View full text Add to dashboard Cite

Nicotine addiction and other forms of drug addiction continue to be significant public health problems in the United States and the rest of the world. Accumulated evidence indicates that brain nicotinic acetylcholine receptors (nAChRs) are a heterogenous family of ion channels expressed in the various parts of the brain. A growing body of preclinical studies suggests that brain nAChRs are critical targets for the development of pharmacotherapies for nicotine and other drug addictions. In this review, we will discuss the nAChR subtypes, their function in response to endogenous brain transmitters, and how their functions are regulated in the presence of nicotine. Furthermore, we will discuss the role of nAChRs in mediating nicotine-induced addictive behavior in animal models. Additionally, we will provide an overview of the effects of nicotine and nicotinic compounds on the mesolimbic dopamine system, part of the reinforcement/reward circuitry of the brain, as an example of the neurochemical basis of nicotine addiction and other drug addictions. An appreciation of the complexity of nicotinic receptors and their regulation will be necessary for the development of nicotinic receptor modulators as potential pharmacotherapy for drug addiction.

show abstract

Effects of Combined Systemic Alcohol and Central Nicotine Administration into Ventral Tegmental Area on Dopamine Release in the Nucleus Accumbens

Cited by 160 publications

References 50 publications

Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking

Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking

Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet

Neuronal Nicotinic Receptors as Brain Targets for Pharmacotherapy of Drug Addiction

Contact Info

Product

Resources

About