title: Protein kinase G increases AMPA receptor GluR1 phosphorylation at serine 845 after repeated cocaine administration in the rat nucleus accumbens.
abstract: The regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit phosphorylation at serine 845 (GluR1-Ser845) by protein kinase G (PKG) activation was investigated in the nucleus accumbens (NAc) after repeated cocaine administration. Intra-NAc injection of the cyclic guanosine monophosphate (cGMP) analog, Rp-8-Br-PET-cGMPS (5 nmol) and the PKG inhibitor, KT5823 (2 nmol), prior to the final drug injection significantly decreased GluR1-Ser845 phosphorylation elevated by repeated systemic injections of cocaine (20mg/kg) once a day for seven consecutive days. The inhibition of PKG also attenuated Ca(2+)-calmodulin-dependent protein kinases II (CaMKII) phosphorylation, however inhibition of CaMKII with KN62 (20 nmol) did not alter the phosphorylation state of GluR1-Ser845. Similarly, inhibition of cGMP or PKG attenuated the repeated cocaine-induced increase in locomotor activity. These findings suggest that the AMPA receptor provides a PKG-sensitive phosphorylation site on GluR1-Ser845 in the NAc after repeated cocaine, thus contributing to behavioral alterations.
authors.affiliation: Department of Biological Sciences, Pusan National University, 63-2 Pusandaehak-ro, Kumjeong-gu, Pusan 609-735, Republic of Korea.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Seo
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Oh
authors.forename: Eun Sang
authors.initials: ES
authors.lastname: Choe
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D003042:Cocaine / Q000633:toxicity; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D003042:Cocaine; D017869:Cyclic GMP-Dependent Protein Kinases; D018091:Receptors, AMPA; D012694:Serine