Artículo
Rubinstein, M.; Cepeda, C.; Hurst, R.S.; Flores-Hernandez, J.; Ariano, M.A.; Falzone, T.L.; Kozell, L.B.; Meshul, C.K.; Bunzow, J.R.; Low, M.J.; Levine, M.S.; Grandy, D.K. "Dopamine D4 receptor-deficient mice display cortical hyperexcitability" (2001) Journal of Neuroscience. 21(11):3756-3763
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Abstract:
The dopamine D4 receptor (D4R) is predominantly expressed in the frontal cortex (FC), a brain region that receives dense input from midbrain dopamine (DA) neurons and is associated with cognitive and emotional processes. However, the physiological significance of this dopamine receptor subtype has been difficult to explore because of the slow development of D4R agonists and antagonists the selectivity and efficacy of which have been rigorously demonstrated in vivo. We have attempted to overcome this limitation by taking a multidimensional approach to the characterization of mice completely deficient in this receptor subtype. Electrophysiological current and clamp recordings were performed in cortical pyramidal neurons voltage-from wild-type and D4R-deficient mice. The frequency of spontaneous synaptic activity and the frequency and duration of paroxysmal discharges induced by epileptogenic agents were increased in mutant mice. Enhanced synaptic activity was also observed in brain slices of wild-type mice incubated in the presence of the selective D4R antagonist PNU-101387G. Consistent with greater electrophysiological activity, nerve terminal glutamate density associated with asymmetrical synaptic contacts within layer VI of the motor cortex was reduced in mutant neurons. Taken together, these results suggest that the D4R can function as an inhibitory modulator of glutamate activity in the FC.
Registro:
| Documento: | Artículo |
| Título: | Dopamine D4 receptor-deficient mice display cortical hyperexcitability |
| Autor: | Rubinstein, M.; Cepeda, C.; Hurst, R.S.; Flores-Hernandez, J.; Ariano, M.A.; Falzone, T.L.; Kozell, L.B.; Meshul, C.K.; Bunzow, J.R.; Low, M.J.; Levine, M.S.; Grandy, D.K. |
| Filiación: | Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Argentina Mental Retardation Research Center, University of California, Los Angeles, CA 90095-1759, United States Department of Neuroscience, Chicago Medical School, North Chicago, IL 60064, United States Department of Behavioral Neuroscience and Research Services, Veterans Administration Medical Center, Oregon Health Sciences University, Portland, OR 97201, United States Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, OR 97201, United States Vollum Institute, Oregon Health Sciences University, Portland, OR 97201, United States Instituto de Investigaciones en Ingeniería Genética y Biologia Molecular, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina Department of Physiology and Pharmacology, L334 Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, United States |
| Palabras clave: | Attention deficit hyperactivity disorder; D4 receptor; Dopamine; Epilepsy; Frontal cortex; Glutamate; dopamine 4 receptor; 4 aminopyridine; bicuculline; convulsant agent; dopamine; dopamine 2 receptor; dopamine 4 receptor; Drd4 protein, mouse; glutamic acid; piperazine derivative; sonepiprazole; sulfonamide; animal experiment; animal model; article; attention deficit disorder; brain cortex; brain slice; controlled study; dopaminergic transmission; drug receptor binding; electrophysiology; epilepsy; frontal cortex; mouse; nerve excitability; nonhuman; priority journal; pyramidal nerve cell; synaptic transmission; animal; cell membrane potential; chemically induced disorder; dose response; drug antagonism; drug effect; genetics; immunohistochemistry; in vitro study; metabolism; motor cortex; mouse mutant; nerve cell inhibition; patch clamp; pathophysiology; seizure; synaptosome; 4-Aminopyridine; Animals; Bicuculline; Cerebral Cortex; Convulsants; Dopamine; Dose-Response Relationship, Drug; Glutamic Acid; Immunohistochemistry; Membrane Potentials; Mice; Mice, Neurologic Mutants; Motor Cortex; Neural Inhibition; Patch-Clamp Techniques; Piperazines; Presynaptic Terminals; Pyramidal Cells; Receptors, Dopamine D2; Receptors, Dopamine D4; Seizures; Sulfonamides |
| Año: | 2001 |
| Volumen: | 21 |
| Número: | 11 |
| Página de inicio: | 3756 |
| Página de fin: | 3763 |
| Título revista: | Journal of Neuroscience |
| Título revista abreviado: | J. Neurosci. |
| ISSN: | 02706474 |
| CODEN: | JNRSD |
| CAS: | dopamine 4 receptor, 137750-34-6; 4 aminopyridine, 1003-40-3, 504-24-5; bicuculline, 485-49-4; dopamine, 51-61-6, 62-31-7; glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; sonepiprazole, 170858-33-0; 4-Aminopyridine, 504-24-5; Bicuculline, 485-49-4; Convulsants; Dopamine, 51-61-6, 137750-34-6; Drd4 protein, mouse; Glutamic Acid, 56-86-0; Piperazines; Receptors, Dopamine D2; Receptors, Dopamine D4, 137750-34-6; Sulfonamides; U 101387, 170858-33-0, 56-86-0 |
| Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v21_n11_p3756_Rubinstein |
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Citas:
---------- APA ----------
Rubinstein, M., Cepeda, C., Hurst, R.S., Flores-Hernandez, J., Ariano, M.A., Falzone, T.L., Kozell, L.B.,..., Grandy, D.K. (2001) . Dopamine D4 receptor-deficient mice display cortical hyperexcitability. Journal of Neuroscience, 21(11), 3756-3763.Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v21_n11_p3756_Rubinstein [ ]
---------- CHICAGO ----------
Rubinstein, M., Cepeda, C., Hurst, R.S., Flores-Hernandez, J., Ariano, M.A., Falzone, T.L., et al. "Dopamine D4 receptor-deficient mice display cortical hyperexcitability" . Journal of Neuroscience 21, no. 11 (2001) : 3756-3763.Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v21_n11_p3756_Rubinstein [ ]
---------- MLA ----------
Rubinstein, M., Cepeda, C., Hurst, R.S., Flores-Hernandez, J., Ariano, M.A., Falzone, T.L., et al. "Dopamine D4 receptor-deficient mice display cortical hyperexcitability" . Journal of Neuroscience, vol. 21, no. 11, 2001, pp. 3756-3763.Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v21_n11_p3756_Rubinstein [ ]
---------- VANCOUVER ----------
Rubinstein, M., Cepeda, C., Hurst, R.S., Flores-Hernandez, J., Ariano, M.A., Falzone, T.L., et al. Dopamine D4 receptor-deficient mice display cortical hyperexcitability. J. Neurosci. 2001;21(11):3756-3763.Available from: https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v21_n11_p3756_Rubinstein [ ]
