Repeated cocaine administration increases nitric oxide efflux in the rat dorsal striatum. 2010

Dong Kun Lee, and Wei Choon Alvin Koh, and Yoon-Bo Shim, and Insop Shim, and Eun Sang Choe
Department of Biological Sciences, Pusan National University, 30 Jangjeon-dong, Kumjeong-gu, Pusan, 609-735, South Korea.

BACKGROUND Repeated injections of cocaine alter extracellular nitric oxide (NO) efflux via interactions between dopamine and glutamate receptor-coupled signaling cascades. OBJECTIVE 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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D007263 Infusions, Parenteral The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping. Intra-Abdominal Infusions,Intraperitoneal Infusions,Parenteral Infusions,Peritoneal Infusions,Infusion, Intra-Abdominal,Infusion, Intraperitoneal,Infusion, Parenteral,Infusion, Peritoneal,Infusions, Intra-Abdominal,Infusions, Intraperitoneal,Infusions, Peritoneal,Intra Abdominal Infusions,Intra-Abdominal Infusion,Intraperitoneal Infusion,Parenteral Infusion,Peritoneal Infusion
D008297 Male Males
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010749 Phosphoprotein Phosphatases A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992) Phosphoprotein Phosphatase,Phosphoprotein Phosphohydrolase,Protein Phosphatase,Protein Phosphatases,Casein Phosphatase,Ecto-Phosphoprotein Phosphatase,Nuclear Protein Phosphatase,Phosphohistone Phosphatase,Phosphoprotein Phosphatase-2C,Phosphoseryl-Protein Phosphatase,Protein Phosphatase C,Protein Phosphatase C-I,Protein Phosphatase C-II,Protein Phosphatase H-II,Protein-Serine-Threonine Phosphatase,Protein-Threonine Phosphatase,Serine-Threonine Phosphatase,Threonine Phosphatase,Ecto Phosphoprotein Phosphatase,Phosphatase C, Protein,Phosphatase C-I, Protein,Phosphatase C-II, Protein,Phosphatase H-II, Protein,Phosphatase, Casein,Phosphatase, Ecto-Phosphoprotein,Phosphatase, Nuclear Protein,Phosphatase, Phosphohistone,Phosphatase, Phosphoprotein,Phosphatase, Phosphoseryl-Protein,Phosphatase, Protein,Phosphatase, Protein-Serine-Threonine,Phosphatase, Protein-Threonine,Phosphatase, Serine-Threonine,Phosphatase, Threonine,Phosphatase-2C, Phosphoprotein,Phosphatases, Phosphoprotein,Phosphatases, Protein,Phosphohydrolase, Phosphoprotein,Phosphoprotein Phosphatase 2C,Phosphoseryl Protein Phosphatase,Protein Phosphatase C I,Protein Phosphatase C II,Protein Phosphatase H II,Protein Phosphatase, Nuclear,Protein Serine Threonine Phosphatase,Protein Threonine Phosphatase,Serine Threonine Phosphatase
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D003042 Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000697 Central Nervous System Stimulants A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. Analeptic,Analeptic Agent,Analeptic Drug,Analeptics,CNS Stimulant,CNS Stimulants,Central Nervous System Stimulant,Central Stimulant,Analeptic Agents,Analeptic Drugs,Central Stimulants,Agent, Analeptic,Agents, Analeptic,Drug, Analeptic,Drugs, Analeptic,Stimulant, CNS,Stimulant, Central,Stimulants, CNS,Stimulants, Central
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001479 Basal Ganglia Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. Basal Nuclei,Ganglia, Basal,Basal Nuclear Complex,Ganglion, Basal,Basal Nuclear Complices,Nuclear Complex, Basal,Nuclei, Basal

Related Publications

Dong Kun Lee, and Wei Choon Alvin Koh, and Yoon-Bo Shim, and Insop Shim, and Eun Sang Choe
January 2010, Neuroscience letters,
Dong Kun Lee, and Wei Choon Alvin Koh, and Yoon-Bo Shim, and Insop Shim, and Eun Sang Choe
February 2010, Neuroscience letters,
Dong Kun Lee, and Wei Choon Alvin Koh, and Yoon-Bo Shim, and Insop Shim, and Eun Sang Choe
April 2003, Journal of neural transmission (Vienna, Austria : 1996),
Dong Kun Lee, and Wei Choon Alvin Koh, and Yoon-Bo Shim, and Insop Shim, and Eun Sang Choe
March 2017, Neuroscience letters,
Dong Kun Lee, and Wei Choon Alvin Koh, and Yoon-Bo Shim, and Insop Shim, and Eun Sang Choe
April 1998, Brain research. Molecular brain research,
Dong Kun Lee, and Wei Choon Alvin Koh, and Yoon-Bo Shim, and Insop Shim, and Eun Sang Choe
July 1993, Journal of neurochemistry,
Dong Kun Lee, and Wei Choon Alvin Koh, and Yoon-Bo Shim, and Insop Shim, and Eun Sang Choe
June 2008, Brain research,
Dong Kun Lee, and Wei Choon Alvin Koh, and Yoon-Bo Shim, and Insop Shim, and Eun Sang Choe
October 2009, Neuroscience,
Dong Kun Lee, and Wei Choon Alvin Koh, and Yoon-Bo Shim, and Insop Shim, and Eun Sang Choe
May 1993, Neuroreport,
Dong Kun Lee, and Wei Choon Alvin Koh, and Yoon-Bo Shim, and Insop Shim, and Eun Sang Choe
March 2002, Synapse (New York, N.Y.),
Copied contents to your clipboard!