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:10.1097/00000374-200203000-00014

Cited by 54 publications

(82 citation statements)

References 50 publications

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“…In contrast, the co-administration of nicotine and alcohol did not result in an additive effect on accumbal DA levels as has been reported previously [70,88]. The difference in the results could be attributed to the difference in the doses of alcohol and nicotine [88] as well as the experimental design where the rats were exposed to either alcohol or nicotine before the co-administration of both alcohol and nicotine [31].…”

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

confidence: 51%

“…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%

“…Thus, in addition to its role as modulator of DA, NT plays a modulatory role on other neurotransmitter systems implicated in addiction to nicotine and alcohol, such as ACh, GABA, and glutamate. Anatomically, NT is co-localized with DAergic [93,94] and GABAergic [95] neurons in the VTA, NA, and PFC [96], areas that have been implicated in drug reward and reinforcement [31,70]. Biochemically, NT increases extracellular GABA in the NA [97].…”

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

confidence: 99%

See 2 more Smart Citations

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

confidence: 51%

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

confidence: 99%

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

confidence: 99%

See 1 more Smart Citation

Novel Therapy for Nicotine Addiction in Alcohol Dependent Rats

Boules¹,

Stennett²,

Muhktar³

et al. 2013

J Addict Res Ther

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“…Corroborating this suggestion, it has been demonstrated that ethanol enhances agonist-induced ion flux through nicotinic receptors (Aistrup et al, 1999;Cardoso et al, 1999) and that ethanol-induced stimulation of mesolimbic dopamine systems involves the activation of nicotinic receptors (Soderpalm et al, 2000). Despite these findings, there have been relatively few animal studies of the basic neurobiology of the combined nicotine and ethanol exposure, and while some studies suggest that nicotine has a modulatory effect on ethanol effects through its cholinergic actions, others show no marked interactions and still others show augmented effects (Bachtell and Ryabinin, 2001;Penland et al, 2001;Tizabi et al, 2002Tizabi et al, , 2003. Accordingly, the role of cholinergic systems in the anxiety alterations associated with nicotine and ethanol adolescent exposure needs to be tested in subsequent studies.…”

Section: Neurobiology Of Nicotine Vs Ethanol Interactionsmentioning

confidence: 99%

Combined Exposure to Nicotine and Ethanol in Adolescent Mice Differentially Affects Anxiety Levels during Exposure, Short-Term, and Long-Term Withdrawal

Abreu‐Villaça

Nunes

Queiroz-Gomes

et al. 2007

Neuropsychopharmacol

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Smoking and consumption of alcoholic beverages are frequently associated during adolescence. This association could be explained by the cumulative behavioral effects of nicotine and ethanol, particularly those related to anxiety levels. However, despite epidemiological findings, there have been few animal studies of the basic neurobiology of the combined exposure in the adolescent brain. In the present work we assessed, through the use of the elevated plus maze, the short-and long-term anxiety effects of nicotine (NIC) and/or ethanol (ETOH) exposure during adolescence (from the 30th to the 45th postnatal day) in four groups of male and female C57BL/6 mice: (1) Concomitant NIC (nicotine free-base solution (50 mg/ml) in 2% saccharin to drink) and ETOH (ethanol solution (25%, 2 g/kg) i.p. injected every other day) exposure; (2) NIC exposure; (3) ETOH exposure; (4) Vehicle. C57BL/6 mice were selected, in spite of the fact that they present slower ethanol metabolism, because they readily consume nicotine in the concentration used in the present study. During exposure (45th postnatal day: PN45), our results indicated that ethanol was anxiolytic in adolescent mice and that nicotine reverted this effect. Short-term drug withdrawal (PN50) elicited sex-dependent effects: exposure to nicotine and/or ethanol was anxiogenic only for females. Although neither nicotine nor ethanol effects persisted up to 1 month postexposure (PN75), the coadministration elicited an anxiogenic response. In spite of the fact that generalizations based on the results from a single strain of mice are prone to shortcomings, our results suggest that the deficient response to the anxiolytic effects of ethanol in adolescents co-exposed to nicotine may drive higher ethanol consumption. Additionally, increased anxiety during long-term smoking and drinking withdrawal may facilitate relapse to drug use.

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“…Activation of nicotinic acetylcholine receptors (nAChRs) is a common event in the pathway used by several addictive drugs to stimulate the mesolimbic DA system, which is a relevant component of the brain stimulation reward pathway [3,4]. Thus, in rats systemic nicotine or alcohol administration elevates extracellular DA levels in the nucleus accumbens, an effect that requires stimulation of nAChRs in this area as well as in the ventral tegmental one, in which the mesolimbic dopaminergic cell bodies are located [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Molecular basis of the selective binding of MDMA enantiomers to the alpha4beta2 nicotinic receptor subtype: Synthesis, pharmacological evaluation and mechanistic studies

Llabrés

García-Ratés

Cristóbal-Lecina

et al. 2014

European Journal of Medicinal Chemistry

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The α4β2 nicotinic acetylcholine receptor (nAChR) is a molecular target of 3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug also known as ecstasy, and it modulates the MDMA-mediated reinforcing properties. However, the enantioselective preference of the α4β2 nAChR subtype still remains unknown. Since the two enantiomers exhibit different pharmacological profiles and stereoselective metabolism, the aim of this study is to assess a possible difference in the interaction of the MDMA enantiomers with this nAChR subtype. To this end, we report a novel simple, yet highly efficient enantioselective synthesis of the MDMA enantiomers, in which the key step is the diastereoselective reduction of imides derived from optically pure tert-butylsulfinamide. The enantioselective binding to the receptor is examined using

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

Cited by 54 publications

References 50 publications

Novel Therapy for Nicotine Addiction in Alcohol Dependent Rats

Novel Therapy for Nicotine Addiction in Alcohol Dependent Rats

Combined Exposure to Nicotine and Ethanol in Adolescent Mice Differentially Affects Anxiety Levels during Exposure, Short-Term, and Long-Term Withdrawal

Molecular basis of the selective binding of MDMA enantiomers to the alpha4beta2 nicotinic receptor subtype: Synthesis, pharmacological evaluation and mechanistic studies

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