The long term goal of this proposal is to be able to isolate genes influencing behavioral and physiological traits elicited by methamphetamine exposure. Quantitative trait locus (QTL) mapping studies in a B6D2F2 population will be performed using PCR of SSLPs with MIT microsatellite markers for traits (thermal responses, exophthalmus, stereotyped behavior and changes in home cage activity) preliminarily mapped in a 25 strain BXD RI study. A QTL is a chromosome site containing a gene or genes which appear to influence these responses to the psychostimulant, methamphetamine. Novel information about the heritability of these traits and the location of the responsible genes will be determined. Due to mouse human genomic synteny, the mapping data should be directly applicable to human research. The proposed mRNA differential display analysis of amphetamine-regulated expression in brain will address the hypothesis that the basis of many drug abuse trait related QTLs are at the expression level. As an aside to the genetic aspect of the experiment, the cloning of genes differentially regulated (through either environmental or genetic mechanisms) by acute and chronic administration of meth-amphetamine will likely yield valuable results relevant at the basic scientific level and possibly clinically as well. Insights into the neural molecular mechanisms that underlie acute and chronic amphetamine action may be gained.
| Hain, H S; Crabbe, J C; Bergeson, S E et al. (2000) Cocaine-induced seizure thresholds: quantitative trait loci detection and mapping in two populations derived from the C57BL/6 and DBA/2 mouse strains. J Pharmacol Exp Ther 293:180-7 |
