the effects of acute cocaine are dampened in animals exposed repeatedly to cocaine due to the increased expression and activity of Cdk5. High Cdk5 activity can also attenuate downstream activation of other cocaine-stimulated signal transduction pathways. When treated acutely with cocaine, mice that overexpress p35 show reduced phosphorylation of ERK and CREB as well as smaller increases in levels of c-fos than do control mice.146
