kn-62 and Amphetamine-Related-Disorders

Amphetamine activates extracellular signal-regulated kinase 1 and 2 (ERK1/2) resulting in cAMP response element-binding protein (CREB) and Elk-1 phosphorylation in striatal neurons. In the present study we investigated whether calcium and calmodulin-dependent protein kinase II (CaMKII) regulates amphetamine-induced ERK1/2 pathways in striatal neurons using Western blot and immunohistochemical analysis. Acute administration of amphetamine (5 mg/kg, i.p.) increased phosphorylated (p)CaMKII immunoreactivity. Inhibition of CaMKII by intrastriatal infusion of KN62 (2, 10, or 25 nmol) attenuated amphetamine-induced increases in pERK1/2, pCREB, and pElk-1 immunoreactivity in the ipsilateral dorsal striatum in a dose-dependent manner. These data suggest that CaMKII controls amphetamine-activated ERK1/2 pathways in striatal neurons in vivo.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Amphetamine; Amphetamine-Related Disorders; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases; Cyclic AMP Response Element-Binding Protein; DNA-Binding Proteins; Dopamine; Dopamine Agents; Dose-Response Relationship, Drug; Enzyme Inhibitors; ets-Domain Protein Elk-1; Immunohistochemistry; Male; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Neostriatum; Neurons; Phosphorylation; Proto-Oncogene Proteins; Rats; Rats, Wistar; Transcription Factors; Up-Regulation