Not all addictive drugs increase Cdk5 activity. Chronic exposure to morphine decreases Cdk5 levels in rat brain.147 Although the effects of in vivo nicotine have not been investigated, in vitro acute nicotine treatments decrease Cdk5-mediated DARPP-32 phosphorylation in mouse striatal slices.148 For psychostimulants and ethanol, Cdk5 appears to serve as a negative regulator of excess dopaminergic activity and may provide a mechanism for dopaminergic homeostasis during repeated exposure to these drugs.
