Intracerebroventricular injections of roscovitine reduce the development of morphine CPP in mice, and heterozygous Cdk5 knockout mice show attenuated development of morphine CPP compared with wild-type controls.151 However, similar to the effects of Cdk5 on locomotor sensitization discussed above, a different result has been observed for cocaine. In conditional Cdk5 knockout mice, cocaine can cause CPP at low doses that do not induce CPP in wild-type mice, suggesting that decreasing Cdk5 activity reduces the threshold for the development of cocaine CPP.152 The findings in conditional knockout mice suggest that Cdk5 reduces cocaine reward and fits well with results from cocaine self-administration studies noted above, in which Cdk5 acts to decrease motivated responding for cocaine.
