Acute Drug Response
In humans, initial sensitivity to psychostimulants has been shown to predict subsequent chronic drug use, and neuroadaptations following repeated use are thought to contribute to drug craving and risk of relapse. Animal models have shown that genetic differences can lead to behavioral differences in acute locomotor activation and chronic locomotor sensitization to psychostimulants. However, identifying the specific genes responsible for these differences has been a challenge.
This Project utilizes the Collaborative Cross (CC) and Diversity Outbred mouse populations to identify genes and gene networks that contribute to phenotypic variation for both acute locomotor sensitivity and sensitization to cocaine. CC lines that exhibit extreme phenotypes will be further characterized to determine whether pharmacokinetic variation is responsible for behavioral differences, or whether cocaine sensitivity correlates with dendritic spine density in the nucleus accumbens. Using an integrative experimental platform we will be able to uncover the biological basis of the relationship between initial drug response, sensitization, neuroadaptation and other addiction related behaviors.