Neurophysiology of Nicotine Addiction.

Department of Neuroscience, Center on Addiction, Learning, Memory, Baylor College of Medicine, Houston, Texas 77030-3498, USA.
Journal of Addiction Research & Therapy (Impact Factor: 1.77). 04/2011; S1(1). DOI: 10.4172/2155-6105.S1-001
Source: PubMed

ABSTRACT Tobacco use is a major health problem, and nicotine is the main addictive component. Nicotine binds to nicotinic acetylcholine receptors (nAChR) to produce its initial effects. The nAChRs subtypes are composed of five subunits that can form in numerous combinations with varied functional and pharmacological characteristics. Diverse psychopharmacological effects contribute to the overall process of nicotine addiction, but two general neural systems are emerging as critical for the initiation and maintenance of tobacco use. Mesocorticolimbic circuitry that includes the dopaminergic pathway originating in the ventral tegmental area and projecting to the nucleus accumbens is recognized as vital for reinforcing behaviors during the initiation of nicotine addiction. In this neural system β2, α4, and α6 are the most important nAChR subunits underlying the rewarding aspects of nicotine and nicotine self-administration. On the other hand, the epithalamic habenular complex and the interpeduncular nucleus, which are connected via the fasciculus retroflexus, are critical contributors regulating nicotine dosing and withdrawal symptoms. In this case, the α5 and β4 nAChR subunits have critical roles in combination with other subunits. In both of these neural systems, particular nAChR subtypes have roles that contribute to the overall nicotine addiction process.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nicotine is the main ingredient of tobacco and it has been described as aversive, reinforce and procognitive. However there is not enough research about the overlapping of the dose-dependent effects as aversive stimulus and precognitive effects. For those reasons we evaluated the nicotine effects on the Conditioned Taste Aversion paradigm (CTA) to measure the dose-response curve of the aversive effects of nicotine and to compare such effects with the procognitive effects reported. 20 male Wistar rats in standard laboratory conditions were randomly assigned to 5 groups (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). The obtained results showed a dose-dependent decrease with a maximum effect at 1.6 mg/kg dose; however we founded effects from the 0.8 mg/kg dose, such dose overlapped with procognitive doses reported. These results allow us to propose that some effects could be due the periferical aversive effects instead of the central procognitive effects.
    04/2013; 3(1):930-940. DOI:10.1016/S2007-4719(13)70943-8
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: An important factor contributing to the high relapse rates among smokers is nicotine withdrawal symptoms. Multiple studies suggest that decreased dopamine release in nucleus accumbens plays a key role in withdrawal. However, recent reports showed that long-term nicotine exposure itself also decreases accumbal dopamine release, suggesting that additional mechanisms are involved in withdrawal. Here, we used real-time cyclic voltammetry in brain slices containing the nucleus accumbens to further elucidate the changes in dopamine release linked to nicotine withdrawal. Rats received vehicle or nicotine via the drinking water for 2–3 months. Studies assessing the expression of somatic signs in vehicle-treated, nicotine-treated, and 24-h nicotine withdrawn rats showed that nicotine withdrawal led to a significant increase in somatic signs. Subsequent voltammetry studies showed that long-term nicotine decreased single-pulse-stimulated dopamine release via an interaction at α6β2* receptors. Nicotine withdrawal led to a partial recovery in α6β2* receptor-mediated release. In addition, long-term nicotine treatment alone increased dopamine release paired-pulse ratios and this was partially reversed with nicotine removal. We then evaluated the effect of bath-applied nicotine and varenicline on dopamine release. Nicotine and varenicline both decreased single-pulse-stimulated release in vehicle-treated, nicotine-treated, and nicotine withdrawn rats. However, bath-applied varenicline increased paired-pulse ratios to a greater extent than nicotine during long-term nicotine treatment and after its withdrawal. Altogether these data suggest that nicotine withdrawal is associated with a partial restoration of dopamine release measures to control levels and that varenicline's differential modulation of dopamine release may contribute to its mechanism of action.
    02/2015; 3(1). DOI:10.1002/prp2.105
  • [Show abstract] [Hide abstract]
    ABSTRACT: Vesicular monoamine transporter-2 (VMAT2) inhibitors reduce methamphetamine (METH) reward in rats. The current study determined the effects of VMAT2 inhibitors lobeline (LOB; 1 or 3 mg/kg) and N-(1,2R-dihydroxylpropyl)-2,6-cis-di(4-methoxyphenethyl)piperidine hydrochloride (GZ-793A; 15 or 30 mg/kg) on METH-induced (0.5 mg/kg, SC) changes in extracellular dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) in the reward-relevant nucleus accumbens (NAc) shell using in vivo microdialysis. The effect of GZ-793A (15 mg/kg) on DA synthesis in tissue also was investigated in NAc, striatum (STR), medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). In NAc shell, METH produced a time-dependent increase in extracellular DA and decrease in DOPAC. Neither LOB nor GZ-793A alone altered extracellular DA; however, both drugs increased extracellular DOPAC. In combination with METH, LOB did not alter the effects of METH on DA; however, GZ-793A, which has greater selectivity than LOB for inhibiting VMAT2, reduced the duration of the METH-induced increase in extracellular DA. Both LOB and GZ-793A enhanced the duration of the METH-induced decrease in extracellular DOPAC. METH also increased tissue DA synthesis in NAc and STR, whereas GZ-793A decreased synthesis; no effect of METH or GZ-793A on DA synthesis was found in mPFC or OFC. These results suggest that selective inhibition of VMAT2 produces a time-dependent decrease in DA release in NAc shell as a result of alterations in tyrosine hydroxylase activity, which may play a role in the ability of GZ-793A to decrease METH reward. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 07/2013; DOI:10.1111/jnc.12373 · 4.24 Impact Factor

Full-text (2 Sources)

Available from
May 30, 2014