Combined effects of systemic alcohol and nicotine on dopamine release in the nucleus accumbens shell

Tizabi, Yousef; Bai, Li; Copeland, Robert L.; Taylor, Robert E.

doi:10.1093/alcalc/agm057

Cited by 115 publications

(98 citation statements)

References 35 publications

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“…Interactions between the drugs may contribute to co-abuse. For example, co-use may enhance reward; co-administration of ethanol and nicotine produces additive effects on dopamine release in the nucleus accumbens, a key component in the reward pathway (Tizabi et al 2007). In addition, the amelioration of the aversive properties of one drug by the other may also contribute to co-abuse.…”

Section: Introductionmentioning

confidence: 99%

Interactive effects of ethanol and nicotine on learning in C57BL/6J mice depend on both dose and duration of treatment

Gulick

Gould

2007

Psychopharmacology

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Objective and rationale-Alcohol and nicotine are commonly co-abused; one possible explanation for co-abuse is that each drug ameliorates the aversive effects of the other. Both drugs have dose-dependent effects on learning and memory. Thus, this study examined the interactive effects of acute ethanol and acute, chronic, or withdrawal from chronic nicotine on fear conditioning in C57BL/6J mice.Materials and methods-Conditioning consisted of auditory conditioned stimulus-foot-shock unconditioned stimulus pairings. For acute studies, saline or ethanol, then saline or nicotine was administered before training, and saline or nicotine was also administered before testing. For chronic and withdrawal studies, saline or nicotine was administered chronically, and ethanol or saline was administered before training.Results-Acute nicotine (0.09 mg/kg) reversed ethanol-induced deficits (1.0 and 1.5 g/kg) in contextual and cued fear conditioning, whereas a low dose of ethanol (0.25 g/kg) reversed nicotine (6.3 mg kg −1 day −1 ) withdrawal-induced deficits in contextual conditioning. Tolerance developed for the effects of nicotine on ethanol-induced deficits in conditioning and cross-tolerance between chronic nicotine and acute ethanol was seen for the enhancing effects of ethanol on conditioning.Conclusions-The complex and sometimes polar actions of ethanol and nicotine on behavior may contribute to co-abuse of these drugs. Specifically, smoking may initially reduce the aversive effects of ethanol, but tolerance develops for this effect. In addition, low doses of alcohol may lessen nicotine withdrawal symptoms.

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Section: Introductionmentioning

confidence: 99%

Interactive effects of ethanol and nicotine on learning in C57BL/6J mice depend on both dose and duration of treatment

Gulick

Gould

2007

Psychopharmacology

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“…In the NAc, acute administration of either ethanol or nicotine causes an increase in dopamine release, in part because of activation of nAChRs in the VTA (Doyon et al, 2013b). Concurrent, acute administration of nicotine and ethanol produces a synergistic effect leading to dopamine release that is significantly higher than that produced by each drug individually (Tizabi et al, 2007). However, when nicotine administration precedes acute alcohol treatment, the ethanol-induced increases in dopamine release are attenuated and dopamine neuronal firing is suppressed in the VTA (Doyon et al, 2013a).…”

Section: Discussionmentioning

confidence: 99%

“…Acute, simultaneous coexposure to ethanol and nicotine produces an additive effect on dopamine release within the nucleus accumbens (NAc) (Tizabi et al, 2007). Interestingly, if nicotine exposure occurs first, the dynamics of dopamine signaling in response to ethanol change.…”

Section: Introductionmentioning

confidence: 99%

Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine

Perez

Quijano-Cardé

Biasi

2015

Neuropsychopharmacol

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Alcohol and nicotine are among the top causes of preventable death in the United States. Unfortunately, people who are dependent on alcohol are more likely to smoke than individuals in the general population. Similarly, smokers are more likely to abuse alcohol. Alcohol and nicotine codependence affects health in many ways and leads to poorer treatment outcomes in subjects who want to quit. This study examined the interaction of alcohol and nicotine during withdrawal and compared abstinence symptoms during withdrawal from one of the two drugs only vs both. Our results indicate that simultaneous withdrawal from alcohol and nicotine produces physical symptoms that are more severe and last longer than those experienced during withdrawal from one of the two drugs alone. In animals experiencing withdrawal after chronic ethanol treatment, acute nicotine exposure was sufficient to prevent abstinence symptoms. Similarly, symptoms were prevented when alcohol was injected acutely in mice undergoing nicotine withdrawal. These experiments provide evidence for the involvement of the nicotinic cholinergic system in alcohol withdrawal. Furthermore, the outcomes of intracranial microinfusions of mecamylamine, a nonselective nicotinic receptor antagonist, highlight a major role for the nicotinic receptors expressed in medial habenula and interpeduncular nucleus during withdrawal. Overall, the data support the notion that modulating the nicotinic cholinergic system might help to maintain long-term abstinence from alcohol.

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“…After collecting three baseline fractions, the animals were pretreated with either saline or NT69L and 40 min later with nicotine (0.5 mg/kg s.c.), alcohol (1 g/kg i.p.) or the combination of the two (the combination doses of nicotine and alcohol were chosen to reflect moderate doses of both drugs that will result in adequate DA release without possible ceiling effect as reported previously [31]. Samples were collected every 20 min over a 3-h period.…”

Section: Surgical Proceduresmentioning

confidence: 99%

“…This part of the brain is strongly implicated in the reinforcing effects of drugs, including alcohol and nicotine [69] and receives heavy dopaminergic input from the ventral tegmental area (VTA). Together the NA and VTA comprise an important component of the mesolimbic 'reward pathway' [31,70]. Acute nicotine elevates dialysate DA levels in the NA [19,71,72].…”

Section: Effect Of Nt69l On Nicotine-and Alcohol-induced Biochemical mentioning

confidence: 99%

Novel Therapy for Nicotine Addiction in Alcohol Dependent Rats

Boules¹,

Stennett²,

Muhktar³

et al. 2013

J Addict Res Ther

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IntroductionNicotine and alcohol addiction are frequently co-morbid problems [1]. The co-dependence of nicotine and alcohol addiction complicates treatment and is often associated with significant morbidity and mortality. Prevalence of smoking in alcoholics is as high as 90% compared to 30% for the general population [2] and alcohol consumption is associated with high nicotine use [3,4]. Co-morbid cigarette smoking and alcoholism has been associated with higher rates of depression in comparison with non-alcoholic smokers [5] and increased cravings for nicotine in comparison with non alcohol dependent smokers [6]. Additionally, smoker alcoholics are more likely to die from smoking related diseases rather than directly from an alcohol related medical condition [7]. Pharmacotherapeutic options for the treatment of alcohol and tobacco co-dependence are limited. Thus, there is a critical need for the development of novel drugs implementing new therapeutic targets.Neurotensin (NT) is a neuropeptide that is closely associated with, and modulates dopamine (DA) [8], acetylcholine (ACh), glutamate, and γ-aminobutyric acid (GABA) neurotransmission, all of which are involved in addiction and reward pathways. Local administration of NT in the prefrontal cortex (PFC) increases extracellular levels of ACh and GABA [9]. Similar data were obtained with the extracranial injection of the NT agonist NT69L [10], a compound that was developed in our laboratory. NT also enhances GABAergic activity in rat hippocampus [11] and reduces glutamatergic neurotransmission in dorsolateral striatum [12]. However, NT must be administered centrally to have an effect because it is easily degraded by peptidases. Our laboratory has developed many NT agonists that can be administered extracranially and mimic the central effects of NT. The most studied of these agonists is NT69L, which binds with equal affinity to the two well-characterized NT receptors, subtype 1 (NTS1) and subtype 2 (NTS2). Our work with NT69L shows that it blocks nicotine-induced sensitization and nicotine self-administration [13][14][15].In addition to its role in animal models for nicotine addiction, the NT system has been strongly implicated in the neurochemical and behavioral effects of alcohol use [16,17]. Chronic administration of NT69L reduces alcohol preference and consumption in mice through modulation of the NTS1 [18]. Biochemically, NT69L normalizes the nicotine-induced changes in DA [19], the neurotransmitter that promotes the motivational process for both nicotine and alcohol, and the alcohol-induced increase in DA and glutamate in the striatum [20]. Additionally, NT modulates other neurotransmitters implicated in alcohol use disorder (AUD). It causes neurochemical changes similar to acamprosate (the calcium salt of acetylhomotaurine), which is one of three FDA-approved drugs to treat AUD. Administration of acamprosate or NT69L increases extracellular concentration of DA in striatum [10,11] and both acamprosate and NT69L modulate glutamate [21,22].Considering the behav...

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Combined effects of systemic alcohol and nicotine on dopamine release in the nucleus accumbens shell

Abstract: These findings further support the hypothesis that an additive effect of alcohol and nicotine on the mesolimbic 'reward pathway' may contribute to the high incidence of smoking in alcoholics. Furthermore, nicotinic antagonists can block such effects of combined alcohol and nicotine.

Cited by 115 publications

References 35 publications

Interactive effects of ethanol and nicotine on learning in C57BL/6J mice depend on both dose and duration of treatment

Interactive effects of ethanol and nicotine on learning in C57BL/6J mice depend on both dose and duration of treatment

Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine

Novel Therapy for Nicotine Addiction in Alcohol Dependent Rats

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