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Titolo:
Dopamine D-4 receptor-deficient mice display cortical hyperexcitability
Autore:
Rubinstein, M; Cepeda, C; Hurst, RS; Flores-Hernandez, J; Ariano, MA; Falzone, TL; Kozell, LB; Meshul, CK; Bunzow, JR; Low, MJ; Levine, MS; Grandy, DK;
Indirizzi:
Univ Buenos Aires, Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol, RA-1428 Buenos Aires, DF, Argentina Univ Buenos Aires BuenosAires DF Argentina RA-1428 Aires, DF, Argentina Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Ciencias Biol, RA-1428Buenos Aires, DF, Argentina Univ Buenos Aires Buenos Aires DF Argentina RA-1428 Aires, DF, Argentina Univ Calif Los Angeles, Mental Retardat Res Ctr, Los Angeles, CA 90095 USAUniv Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Chicago Med Sch, Dept Neurosci, N Chicago, IL 60064 USA Chicago Med Sch NChicago IL USA 60064 Neurosci, N Chicago, IL 60064 USA Vet Adm Med Ctr, Dept Behav Neurosci, Portland, OR 97201 USA Vet Adm Med Ctr Portland OR USA 97201 av Neurosci, Portland, OR 97201 USA Vet Adm Med Ctr, Res Serv, Portland, OR 97201 USA Vet Adm Med Ctr Portland OR USA 97201 r, Res Serv, Portland, OR 97201 USA Oregon Hlth Sci Univ, Vollum Inst, Portland, OR 97201 USA Oregon Hlth Sci Univ Portland OR USA 97201 m Inst, Portland, OR 97201 USA Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA Oregon Hlth Sci Univ Portland OR USA 97201 rmacol, Portland, OR 97201 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 11, volume: 21, anno: 2001,
pagine: 3756 - 3763
SICI:
0270-6474(20010601)21:11<3756:DDRMDC>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
HYPERACTIVITY DISORDER; NOVELTY SEEKING; D4 RECEPTORS; PREFRONTAL CORTEX; GENE; POLYMORPHISM; ASSOCIATION; ANTAGONIST; MODULATION; CLOZAPINE;
Keywords:
dopamine; D-4 receptor; frontal cortex; glutamate; epilepsy; attention deficit hyperactivity disorder;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Rubinstein, M Univ Buenos Aires, Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol, Vuelta Obligado 2490, RA-1428 Buenos Aires, DF,Argentina Univ Buenos Aires Vuelta Obligado 2490 Buenos Aires DF ArgentinaRA-1428
Citazione:
M. Rubinstein et al., "Dopamine D-4 receptor-deficient mice display cortical hyperexcitability", J NEUROSC, 21(11), 2001, pp. 3756-3763

Abstract

The dopamine D-4 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 hasbeen 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 voltage-clamp recordings were performed in cortical pyramidal neurons 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 ofthe 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 reducedin mutant neurons. Taken together, these results suggest that the D4R can function as an inhibitory modulator of glutamate activity in the FC.

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Documento generato il 20/01/20 alle ore 15:56:32