An animal model of differential genetic risk for methamphetamine intake

摘要: The question of whether genetic factors contribute to risk for methamphetamine (MA) use and dependence has not been intensively investigated. Compared human populations, animal models offer the advantages control over family history drug exposure. Using selective breeding, we created lines mice that differ in voluntary MA intake identified chromosomal addresses contributory genes. A quantitative trait locus was on chromosome 10 accounts more than 50% variance selected mouse lines. In addition, behavioral physiological screening differences corresponding with have generated hypotheses are testable humans. Heightened sensitivity aversive certain effects MA, such as MA-induced reduction body temperature, hallmarks bred low intake. Furthermore, unlike MA-avoiding mice, MA-preferring sensitive rewarding reinforcing effects, increases brain extracellular dopamine levels. Gene expression analyses implicate importance a network enriched transcription factor genes, some which regulate mu opioid receptor gene, Oprm1, use. Neuroimmune appear play role differential response between high candidate gene studies provide strong support trace amine associated 1 Taar1, polymorphism is amine-associated (TAAR1) agonist, non-functional Taar1 allele segregates consumption. Thus, reduced TAAR1 function potential increase Overall, existing findings drinking powerful model identifying involved determining harmful Future directions include development binge intake, examining effect withdrawal from chronic studying x environment interactions. These other intended improve our regard its translational value addiction.