Abstract:
Brain dopamine (DA) systems are involved in the modulation of the sensorimotor gating phenomenon known as prepulse inhibition (PPI). The class of D 2 -like receptors, including the D2, D3, and D4 receptor subtypes, have all been implicated in the control of PPI via studies of DA agonists and antagonists in rats. Nevertheless, the functional relevance of each receptor subtype remains unclear because these ligands are not specific. To determine the relevance of each receptor subtype, we used genetically altered strains of 'knock-out' mice lacking the DA D2, D3, or D4 receptors. We tested the effects of each knock-out on both the phenotypic expression of PPI and the disruption of PPI produced by the indirect DA agonist d-amphetamine (AMPH). No phenotypic differences in PPI were observed at baseline. AMPH significantly disrupted PPI in the D2 (+/+) mice but had no effect in the D2 (-/-) mice. After AMPH treatment, both DA D3 and D4 receptor (+/+) and (-/-) mice had significant disruptions in PPI. These findings indicate that the AMPH-induced disruption of PPI is mediated via the DA D2 receptor and not the D3 or D4 receptor subtypes. Uncovering the neural mechanisms involved in PPI will further our understanding of the substrates of sensorimotor gating and could lead to better therapeutics to treat gating disorders, such as schizophrenia.
Registro:
Documento: |
Artículo
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Título: | The dopamine D 2 , but not D 3 or D 4 , receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice |
Autor: | Ralph, R.J.; Varty, G.B.; Kelly, M.A.; Wang, Y.-M.; Caron, M.G.; Rubinstein, M.; Grandy, D.K.; Low, M.J.; Geyer, M.A. |
Filiación: | Department of Neuroscience, Univ. of California at San Diego, San Diego, CA 92093-0804, United States Department of Psychiatry, Univ. of California at San Diego, San Diego, CA 92093-0804, United States Vollum Institute, Oregon Health Sciences University, Portland, OR 97201, United States Dept. of Physiology and Pharmacology, Oregon Health Sciences University, Portland, OR 97201, United States Howard Hughes Med. Inst. Labs., Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, United States Inst. Invest. Ing. Genet. y Biol. M., Consejo Nac. Investigiones Cie. y T., Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
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Palabras clave: | Amphetamine; Dopamine receptors; Genetics; Mice; Prepulse inhibition; Startle; dexamphetamine; dopamine; dopamine 2 receptor; dopamine 3 receptor; dopamine 4 receptor; ligand; neuroleptic agent; receptor subtype; amphetamine; dopamine 2 receptor; dopamine 3 receptor; dopamine 4 receptor; dopamine receptor; dopamine receptor stimulating agent; Drd3 protein, mouse; Drd4 protein, mouse; animal experiment; article; controlled study; drug mechanism; female; genotype; knockout mouse; male; mouse; nonhuman; phenotype; prepulse inhibition; priority journal; schizophrenia; sensorimotor function; startle reflex; animal; auditory stimulation; drug effect; mouse mutant; nerve cell inhibition; startle reflex; Acoustic Stimulation; Amphetamine; Animals; Dopamine Agents; Mice; Mice, Knockout; Mice, Mutant Strains; Neural Inhibition; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Dopamine D4; Startle Reaction |
Año: | 1999
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Volumen: | 19
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Número: | 11
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Página de inicio: | 4627
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Página de fin: | 4633
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Título revista: | Journal of Neuroscience
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Título revista abreviado: | J. Neurosci.
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ISSN: | 02706474
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CODEN: | JNRSD
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CAS: | dexamphetamine, 1462-73-3, 51-63-8, 51-64-9; dopamine 4 receptor, 137750-34-6; dopamine, 51-61-6, 62-31-7; amphetamine, 1200-47-1, 139-10-6, 156-34-3, 2706-50-5, 300-62-9, 51-62-7, 60-13-9, 60-15-1; Amphetamine, 300-62-9; Dopamine Agents; Drd3 protein, mouse; Drd4 protein, mouse; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Dopamine D4, 137750-34-6
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v19_n11_p4627_Ralph |
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Citas:
---------- APA ----------
Ralph, R.J., Varty, G.B., Kelly, M.A., Wang, Y.-M., Caron, M.G., Rubinstein, M., Grandy, D.K.,..., Geyer, M.A.
(1999)
. The dopamine D 2 , but not D 3 or D 4 , receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice. Journal of Neuroscience, 19(11), 4627-4633.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v19_n11_p4627_Ralph [ ]
---------- CHICAGO ----------
Ralph, R.J., Varty, G.B., Kelly, M.A., Wang, Y.-M., Caron, M.G., Rubinstein, M., et al.
"The dopamine D 2 , but not D 3 or D 4 , receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice"
. Journal of Neuroscience 19, no. 11
(1999) : 4627-4633.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v19_n11_p4627_Ralph [ ]
---------- MLA ----------
Ralph, R.J., Varty, G.B., Kelly, M.A., Wang, Y.-M., Caron, M.G., Rubinstein, M., et al.
"The dopamine D 2 , but not D 3 or D 4 , receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice"
. Journal of Neuroscience, vol. 19, no. 11, 1999, pp. 4627-4633.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v19_n11_p4627_Ralph [ ]
---------- VANCOUVER ----------
Ralph, R.J., Varty, G.B., Kelly, M.A., Wang, Y.-M., Caron, M.G., Rubinstein, M., et al. The dopamine D 2 , but not D 3 or D 4 , receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice. J. Neurosci. 1999;19(11):4627-4633.
Available from: https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v19_n11_p4627_Ralph [ ]