title: Protein kinase G linked to dopamine D3 receptors in the dorsal striatum controls dopamine release, ΔFosB expression and locomotor activity after repeated cocaine administration.
abstract: Protein kinase G (PKG) has been implicated in a variety of physiological functions including synaptic plasticity in the brain. This study investigated the involvement of dopamine D3 (D3) receptors in PKG-regulated dopamine release, long-term changes in gene expression and behavioral sensitization after repeated cocaine administration. Repeated systemic injections of cocaine (20mg/kg), once a day for seven consecutive days, increased extracellular dopamine concentrations in the dorsal striatum. Inhibition of neuronal nitric oxide synthase, cGMP or PKG, stimulation of D3 receptors, and simultaneous inhibition of each of them with D3 receptor stimulation decreased the repeated cocaine-induced increase in dopamine concentrations and locomotor activity. Similarly, inhibition of PKG and simultaneous inhibition of PKG with D3 receptor stimulation decreased ΔFosB immunoreactivity elevated by repeated cocaine administration, however stimulation of D3 receptors alone did not. These findings suggest that activation of PKG after repeated cocaine administration is more sensitive to interact with D3 receptors in the dopamine terminals than those in medium spiny neurons. This interaction may result in the development of behavioral sensitization by the upregulation of dopamine releases in the dorsal striatum.
authors: Department of Biological Sciences, Pusan National University, 63-2 Pusandaehak-ro, Kumjeong-gu, Pusan 609-735, Republic of Korea.
authors: Dong Kun
authors: DK
authors: Lee
authors: Jeong Hwan
authors: JH
authors: Oh
authors: Ju Hwan
authors: JH
authors: Yang
authors: Buhyun
authors: B
authors: Youn
authors: Yoon-Bo
authors: YB
authors: Shim
authors: Insop
authors: I
authors: Shim
authors: John Q
authors: JQ
authors: Wang
authors: Eun Sang
authors: ES
authors: Choe
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000037:antagonists & inhibitors; D062965:Cyclic GMP-Dependent Protein Kinase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004789:Enzyme Activation; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000819:agonists / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D000697:Central Nervous System Stimulants; C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D050637:Receptors, Dopamine D3; D017661:Receptors, Presynaptic; D052248:Nitric Oxide Synthase Type I; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D011493:Protein Kinase C; D006152:Cyclic GMP; D003042:Cocaine; D004298:Dopamine