Project 2: The Methamphetamine-sensitive Circadian Oscillator

Dr. Michael Menaker and Dr. Gene Block, Project Leaders

In order to validate chemical tools, we will begin by evaluating the effects of known pharmacological agents on the circadian system. We have shown consistent and robust effects of chronic exposure to methamphetamine on circadian period and activity/rest ratio in intact mice. These effects are dose and strain dependent. We will investigate the responses to the drug of mice carrying each of the known circadian mutations both in terms of their behavior and the electrophysiology of the SCN in vivo and in vitro. In addition to their intrinsic interest and their bearing on the mechanisms of action of addictive drugs, these studies will provide proof of principle for in vivo validation of the circadian effects of small molecules derived from circadian screens.