Browsing by Subject "Nicotinic receptors"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    CHRNB3 is more strongly associated with Fagerström test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results
    (Wiley, 2012) Rice, John P.; Hartz, Sarah M.; Agrawal, Arpana; Almasy, Laura; Bennett, Siiri; Breslau, Naomi; Bucholz, Kathleen K.; Doheny, Kimberly F.; Edenberg, Howard J.; Goate, Alison M.; Hesselbrock, Victor; Howells, William B.; Johnson, Eric O.; Kramer, John; Krueger, Robert F.; Kuperman, Samuel; Laurie, Cathy; Manolio, Teri A.; Neuman, Rosalind J.; Nurnberger, John I.; Porjesz, Bernice; Pugh, Elizabeth; Ramos, Erin M.; Saccone, Nancy; Saccone, Scott; Schuckit, Marc; Bierut, Laura J.; GENEVA Consortium; Biochemistry and Molecular Biology, School of Medicine
    Aims: Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e., CPD versus Fagerström test for cigarette dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence. Design: Genome-wide association study. Setting: Community sample. Participants: A total of 3365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2267 were European Americans, 999 were African Americans. Measurements: Nicotine dependence defined by FTCD score ≥4, CPD. Findings: The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 [odds ratio (OR) = 0.65, P = 2.4 × 10(-8) ]. This association was further strengthened in a meta-analysis with a previously published data set (combined P = 6.7 × 10(-16) , total n = 4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (β = -0.08, P = 0.0004). Conclusions: Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci.
  • Thumbnail Image
    Item
    Nicotine Use in Schizophrenia: a part of the cure or the disease?
    (2012-03-16) Berg, Sarah A.; Chambers, R. Andrew; Czachowski, Cristine L.; Grahame, Nicholas J.; Breier, Alan, 1953-
    Nicotine use among individuals with schizophrenia occurs at extremely high rates. The prevailing theory is that individuals with schizophrenia smoke as a form of self-medication to ameliorate sensory and cognitive deficits. However, these individuals also have enhanced rates of addiction to several drugs of abuse and may therefore smoke as a result of enhanced addiction liability. The experiments described herein explored these two hypotheses by assessing the effect that nicotine has on working memory, addiction vulnerability (locomotor sensitization and self-administration), and nicotinic acetylcholine receptor (nAChR) expression as well as the developmental expression of these characteristics in the neonatal ventral hippocampal (NVHL) neurodevelopmental animal model of schizophrenia. The results from these studies indicate that NVHLs had working memory impairments in both adolescence and adulthood, with nicotine having a negligible effect. Additionally, NVHLs displayed enhanced locomotor sensitization to nicotine which emerged in adulthood as well as an enhanced acquisition of nicotine self-administration, administering more nicotine overall. These behavioral differences cannot be attributed to nAChR expression as nicotine upregulated nAChR to a similar extent between NVHL and SHAM control animals. These data indicate that the enhanced rates of nicotine use among individuals with schizophrenia may occur as a result of an enhanced vulnerability to nicotine addiction.