Date of Award
2008
Degree Type
Thesis
Degree Name
Master of Science
Program
Biology
Supervisor
Dr. Shiva Singh
Second Advisor
Dr. Kathleen Hill
Third Advisor
Dr. André Lachance
Abstract
Attempts to discover the genetic determinants of alcohol and nicotine addiction have been underway for many years. A common site of action for both nicotine and alcohol effects are neuronal nicotinic acetylcholine receptors (nAChR). This thesis deals with the molecular analysis of four nAChR subunits {Chrna4, Chrnb2, Chma5, and Chrna7) and their relationship with alcohol preference (AP) in mice. The alcohol- preferring C57BL∕6J (B6) and alcohol-avoiding DBA∕2J (D2) strains of mice provide a well established genetic model for the study of AP. Semi-quantitative RT-PCR was used to assess πAChR gene expression in the brains of B6 and D2 mice with and without ethanol treatment. Further studies involved SNP association analysis in the F2 generations produced from reciprocal crosses of the B6 and D2 strains, as well as BXD recombinant inbred lines. The gene expression results show that Chrna4 is ethanol responsive in the B6 strain, whereas Chrna5 is strain-specific ethanol-responsive. The F2 segregation results strongly suggest that Chrna5 is associated with AP in mice. Moreover, the data indicate that there may be grandparent-of-origin effects influencing the inheritance of the Chrnb2 genotype. Data on the BXD RI lines did not support a role for nAChRs in AP, however this analysis was limited by the absence of high ethanol preferring lines. The results presented here are novel and identify Chrna5 as a strong candidate for involvement in the AP phenotype in mice.
Recommended Citation
Symons, Melissa Nicole, "NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS AND ALCOHOL PREFERENCE IN MICE: ANALYSES OF BRAIN GENE EXPRESSION AND CO-SEGREGATION STUDIES" (2008). Digitized Theses. 4323.
https://ir.lib.uwo.ca/digitizedtheses/4323