Dopamine D receptor antagonists alter autophosphorylation of focal adhesion kinases in the mouse forebrain in vivo.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase expressed in neurons of the developing and adult brain in addition to non-neuronal cells. Activation of FAK is initiated by autophosphorylation of the kinase at tyrosine 397 (Y397). Active FAK transmits extracellular signals inside neurons to integrate cytoskeletal rearrangements and modulate synaptic transmission and plasticity. Here we investigated roles of dopamine receptors, i.e., G-coupled D and G-coupled D subtypes, in regulation of FAK autophosphorylation in two major dopamine-innervated areas of the mouse brain in vivo. We found that acute systemic administration of a dopamine D or D receptor agonist had no effect on basal FAK autophosphorylation at Y397 in the striatum and medial prefrontal cortex (mPFC). Similarly, a D receptor antagonist did not alter striatal and cortical Y397 phosphorylation. However, acute injection of a D receptor antagonist (eticlopride or haloperidol) induced a marked increase in Y397 phosphorylation in the striatum and mPFC. The eticlopride-induced Y397 phosphorylation can be seen in the two striatal subdivisions, the caudate putamen and nucleus accumbens, and was induced at two effective doses (0.1 and 0.5 mg/kg). All drug treatments caused insignificant changes in cellular FAK protein expression. These results reveal an existence of a tonic inhibitory tone of dopamine D receptors over basal FAK autophosphorylation in the mouse striatum and mPFC.