Figure 4.

Drd1a-agonist or l-DOPA activation of ERK1/2 in the dopamine (DA)-depleted striatum does not involve DARPP-32. Comparison of coronal brain sections at the level of the rostral striatum from wild-type and DARPP-32 KO mice, with unilateral lesions of the nigrostriatal dopamine system and treated with a Drd1a agonist (SKF-81297; 5 mg/kg; 1 d) or l-DOPA (20 mg/kg with 12 mg/kg benserazide; 10 d). DARPP-32-IR labels neurons in the striatum in wild-type mice, which are unlabeled in DARPP-32 KO mice. Unilateral lesion of the nigrostriatal dopamine pathway in these animals is shown by the absence of TH-IR in the axonal terminals in the right striatum. Activation of ERK1/2 in response to either Drd1a agonist treatment (left images) or l-DOPA treatment (right images) is demonstrated by phospho-ERK1/2-IR throughout the dopamine-depleted striatum. High-power images from the dorsolateral striatum (inset boxes; 100 μm wide) show few to no phospho-ERK1/2-immunoreactive neurons in the DA-intact striatum. In contrast, there are numerous phospho-ERK1/2-immunoreactive neurons in the DA-depleted striatum in both the wild-type and DARPP-32 KO animals.