Psychopharmacology · 2009
Repeated cocaine administration increases nitric oxide efflux in the rat dorsal striatum.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Lee Dong Kun, Koh Wei Choon Alvin, Shim Yoon-Bo, Shim Insop, Choe Eun Sang
Аннотация
RATIONALE: Repeated injections of cocaine alter extracellular nitric oxide (NO) efflux via interactions between dopamine and glutamate receptor-coupled signaling cascades.
OBJECTIVES: Putative cellular mechanisms underlying changes in NO efflux following repeated cocaine administration were investigated.
METHODS: Real-time detection of NO efflux using a NO biosensor was mainly performed in the rat dorsal striatum in vivo.
RESULTS: Repeated exposure to cocaine (20 mg/kg), once a day for seven consecutive days, increased NO levels. Repeated injections of cocaine also increased the phosphorylation of neuronal nitric oxide synthase (nNOS), and inhibition of nNOS decreased the repeated cocaine-evoked increases in NO levels. Inhibition of protein kinase A, but not protein phosphatases, synergistically increased NO levels elevated by repeated cocaine injections. Blockade of dopamine D1 (D1) receptors or stimulation of dopamine D2 (D2) receptors decreased the repeated cocaine-evoked increases in NO levels. Similarly, blockade of N-methyl-D: -aspartate (NMDA) receptors and group I metabotropic glutamate receptors (mGluRs) or stimulation of group III mGluRs also decreased the repeated cocaine-evoked increases in NO levels.
CONCLUSION: Stimulation of D1 receptors or group I mGluRs following repeated cocaine administration upregulates NO efflux via an NMDA receptor-evoked Ca2+ influx, while stimulation of D2 receptors or group III mGluRs downregulates NO efflux. Dephosphorylation of phosphorylated nNOS by protein phosphatases is necessary for upregulating NO efflux in the dorsal striatum after repeated cocaine administration.
OBJECTIVES: Putative cellular mechanisms underlying changes in NO efflux following repeated cocaine administration were investigated.
METHODS: Real-time detection of NO efflux using a NO biosensor was mainly performed in the rat dorsal striatum in vivo.
RESULTS: Repeated exposure to cocaine (20 mg/kg), once a day for seven consecutive days, increased NO levels. Repeated injections of cocaine also increased the phosphorylation of neuronal nitric oxide synthase (nNOS), and inhibition of nNOS decreased the repeated cocaine-evoked increases in NO levels. Inhibition of protein kinase A, but not protein phosphatases, synergistically increased NO levels elevated by repeated cocaine injections. Blockade of dopamine D1 (D1) receptors or stimulation of dopamine D2 (D2) receptors decreased the repeated cocaine-evoked increases in NO levels. Similarly, blockade of N-methyl-D: -aspartate (NMDA) receptors and group I metabotropic glutamate receptors (mGluRs) or stimulation of group III mGluRs also decreased the repeated cocaine-evoked increases in NO levels.
CONCLUSION: Stimulation of D1 receptors or group I mGluRs following repeated cocaine administration upregulates NO efflux via an NMDA receptor-evoked Ca2+ influx, while stimulation of D2 receptors or group III mGluRs downregulates NO efflux. Dephosphorylation of phosphorylated nNOS by protein phosphatases is necessary for upregulating NO efflux in the dorsal striatum after repeated cocaine administration.
Предметные рубрики MeSH
AnimalsBasal GangliaBiosensing TechniquesCentral Nervous System StimulantsCocaineCyclic AMP-Dependent Protein KinasesDopamine AgonistsDopamine AntagonistsEnzyme InhibitorsExcitatory Amino Acid AgonistsExcitatory Amino Acid AntagonistsInfusions, ParenteralMaleNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IPhosphoprotein PhosphatasesPhosphorylationRatsRats, Sprague-DawleyReceptors, Dopamine D1Receptors, Dopamine D2Receptors, Metabotropic GlutamateReceptors, N-Methyl-D-AspartateSignal TransductionTime Factors