title: Dopamine D4 receptors linked to protein kinase G are required for changes in dopamine release followed by locomotor activity after repeated cocaine administration.
abstract: We previously found that the dopamine D2-type receptors (D2 and D3 receptors), coupled to protein kinase G (PKG), upregulate locomotor activity after repeated cocaine administration. In this study, D4 receptors, another type of D2 receptor also coupled to PKG, were examined to determine their requirement in the regulation of locomotor activity after repeated cocaine administration. The results demonstrated that repeated injections of cocaine (20 mg/kg), given once a day for seven consecutive days, significantly increased extracellular dopamine concentrations. Intra-caudate infusion of the D4 receptor agonist, PD168077 (10 nmol), and the PKG inhibitor, KT5823 (2 nmol), significantly decreased the repeated cocaine-induced increase in dopamine levels and locomotor activity. However, intra-caudate infusion of KT5823, but not PD168077, decreased ∆FosB immunoreactivity elevated by repeated cocaine administration. These findings suggest that D4 receptors linked to PKG could be a key modulator for dopamine release required for changes in locomotor activity caused by repeated cocaine exposure.
authors.affiliation: Department of Biological Sciences, Pusan National University, 63-2 Pusandaehak-ro, Kumjeong-gu, Pusan, 609-735, Korea.
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Oh
authors.forename: Dong Kun
authors.initials: DK
authors.lastname: Lee
authors.forename: Yoon-Bo
authors.initials: YB
authors.lastname: Shim
authors.forename: In Soo
authors.initials: IS
authors.lastname: Ryu
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Seo
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.forename: Ju Hwan
authors.initials: JH
authors.lastname: Yang
authors.forename: Hyun-Wook
authors.initials: HW
authors.lastname: Cho
authors.forename: Eun Sang
authors.initials: ES
authors.lastname: Choe
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050638:Receptors, Dopamine D4 / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001549:Benzamides; D002227:Carbazoles; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; C483820:Fosb protein, rat; C477501:N-((4-(2-cyanophenyl)-1-piperazinyl)methyl)-3-methylbenzamide; D010879:Piperazines; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C073601:KT 5823; D050638:Receptors, Dopamine D4; D052248:Nitric Oxide Synthase Type I; D014446:Tyrosine 3-Monooxygenase; D017869:Cyclic GMP-Dependent Protein Kinases; D003042:Cocaine; D004298:Dopamine