Article

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.

Full-text

Available from: John Broussard, Jun 14, 2015
0 Followers
 · 
162 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cigarette smoking is the leading preventable cause of death in the Western world, with a considerably higher prevalence observed in schizophrenia compared to the general population. Despite the negative health consequences of smoking heavily, it has been proposed that individuals with schizophrenia may maintain smoking behaviours to remediate symptoms associated with the disorder. Neurocognitive deficits are a core feature of schizophrenia and are present in approximately 80% of patients. Further, these deficits constitute an endophenotype of schizophrenia, as they are stable across disease phases, and heritable. The neurocognitive deficits that are present in schizophrenia are especially debilitating, since they are associated with poor clinical and functional outcomes and community integration. Interestingly, these deficits may also constitute a vulnerability factor towards the initiation and maintenance of tobacco use. Contributing to the potential shared vulnerability between schizophrenia and tobacco dependence is a dysregulation of the nicotinic acetylcholine receptor (nAChR) system. Pre-clinical evidence has shown that nicotine affects several neurotransmitter systems, including dopamine (DA), glutamate, and γ-aminobutyric acid (GABA), and certain neuropsychological deficits associated with these neurotransmitters (reaction time, spatial working memory, sustained attention, and sensory gating) are improved after nicotine administration in patients with schizophrenia. These positive effects on neurocognition appear to be more pronounced in smokers with schizophrenia, and may be an important mechanism that explains the co-morbidity of schizophrenia and tobacco dependence.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 07/2013; DOI:10.1016/j.pnpbp.2013.07.010 · 4.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tobacco-related behaviors and the underlying addiction to nicotine are complex tangles of genetic and environmental factors. Efforts to understand the genetic component of these traits have identified sites in the genome (Single Nucleotide Polymorphisms, or SNPs) that might account for some part of the role of genetics in nicotine addiction. Encouragingly, some of these candidate SNPs remain significant in meta-analyses. However, genetic associations cannot be fully assessed, regardless of statistical significance, without an understanding of the functional consequences of the alleles present at these SNPs. The proper experimental test for allelic function can be very difficult to define, representing a roadblock in translating genetic results into treatment to prevent smoking and other nicotine-related behaviors. This roadblock can be navigated in part with a new web-based tool, the Encyclopedia of DNA Elements (ENCODE). ENCODE is a compilation of searchable data on several types of biochemical functions or “marks” across the genome. These data can be queried for the co-localization of a candidate SNP and a biochemical mark. The presence of a SNP within a marked region of DNA enables the generation of better-informed hypotheses to test possible functional roles of alleles at a candidate SNP. Two examples of such co-localizations are presented. One example reveals ENCODE’s ability to relate a candidate SNP’s function with a gene very far from the physical location of the SNP. The second example reveals a new potential function of the SNP, rs4105144, that has been genetically associated with the number of cigarettes smoked per day. Details for accessing the ENCODE data for this SNP are provided to serve as a tutorial. By serving as a bridge between genetic associations and biochemical function, ENCODE has the power to propel progress in untangling the genetic aspects of nicotine addiction—a major public health concern.
    Pharmacology Biochemistry and Behavior 08/2014; 123. DOI:10.1016/j.pbb.2014.01.009 · 2.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adolescence is a unique period of development characterized by enhanced tobacco use and long-term vulnerability to neurochemical changes produced by adolescent nicotine exposure. In order to understand the underlying mechanisms that contribute to developmental differences in tobacco use, this study compared changes in cholinergic transmission during nicotine exposure and withdrawal in naïve adult rats compared to (1) adolescent rats and (2) adult rats that were pre-exposed to nicotine during adolescence. The first study compared extracellular levels of acetylcholine (ACh) in the nucleus accumbens (NAc) during nicotine exposure and precipitated withdrawal using microdialysis procedures. Adolescent (postnatal day, PND, 28-42) and adult rats (PND60-74) were prepared with osmotic pumps that delivered nicotine for 14 days (adolescents 4.7 mg/kg/day; adults 3.2 mg/kg/day; expressed as base). Another group of adults was exposed to nicotine during adolescence and then again in adulthood (pre-exposed adults) using similar methods. Control rats received a sham surgery. Following 13 days of nicotine exposure, the rats were implanted with microdialysis probes in the NAc. The following day, dialysis samples were collected during baseline and following systemic administration of the nicotinic receptor antagonist mecamylamine (1.5 and 3.0 mg/kg, i.p.) to precipitate withdrawal. A second study compared various metabolic differences in cholinergic transmission using the same treatment procedures as the first study. Following 14 days of nicotine exposure, the NAc was dissected and acetylcholinesterase (AChE) activity was compared across groups. In order to examine potential group differences in nicotine metabolism, blood plasma levels of cotinine (a nicotine metabolite) were also compared following 14 days of nicotine exposure. The results from the first study revealed that nicotine exposure increased baseline ACh levels to a greater extent in adolescent versus adult rats. During nicotine withdrawal, ACh levels in the NAc were increased in a similar manner in adolescent versus adult rats. However, the increase in ACh that was observed in adult rats experiencing nicotine withdrawal was blunted in pre-exposed adults. These neurochemical effects do not appear to be related to nicotine metabolism, as plasma cotinine levels were similar across all groups. The second study revealed that nicotine exposure increased AChE activity in the NAc to a greater extent in adolescent versus adult rats. There was no difference in AChE activity in pre-exposed versus naïve adult rats. In conclusion, our results suggest that nicotine exposure during adolescence enhances baseline ACh in the NAc. However, the finding that ACh levels were similar during withdrawal in adolescent and adult rats suggests that the enhanced vulnerability to tobacco use during adolescence is not related to age differences in withdrawal-induced increases in cholinergic transmission. Our results also suggest that exposure to nicotine during adolescence suppresses withdrawal-induced increases in cholinergic responses during withdrawal. Taken together, this report illustrates important short- and long-term changes within cholinergic systems that may contribute to the enhanced susceptibility to tobacco use during adolescence. © 2014 S. Karger AG, Basel.
    Developmental Neuroscience 05/2014; 36(3-4). DOI:10.1159/000360133 · 2.45 Impact Factor