Dopamine D4 receptor knockout mice exhibit neurochemical changes consistent with decreased dopamine release

Theresa Currier Thomas; Paul J. Kruzich; B. Matthew Joyce; C. R. Gash; Katherine Suchland; Stewart P. Surgener; Erin C. Rutherford; David K. Grandy; Greg A. Gerhardt; Paul E.A. Glaser

doi:10.1016/j.jneumeth.2007.03.009

Dopamine D4 receptor knockout mice exhibit neurochemical changes consistent with decreased dopamine release

Theresa Currier Thomas, Paul J. Kruzich, B. Matthew Joyce, C. R. Gash, Katherine Suchland, Stewart P. Surgener, Erin C. Rutherford, David K. Grandy, Greg A. Gerhardt, Paul E.A. Glaser

Producción científica: Article › revisión exhaustiva

28 Citas (Scopus)

Resumen

Dopamine D4 receptor (D4R) knockout mice (D4R-/-) provided for unique neurochemical studies designed to understand D4R contributions to dopamine (DA) regulation. In this study, post-mortem brain tissue content of DA did not differ between D4R+/+ and D4R-/- mice in the striatum (Str) or nucleus accumbens core (NAc). However, there was a significant decrease (82%) in the content of 3,4-dihydoxyphenylacetic acid (DOPAC), a major metabolite of DA, in the NAc of D4R-/- mice. Microdialysis studies performed in a region of brain spanning of the dorsal Str and NAc showed lower baseline levels of DA and a significant reduction in KCl-evoked overflow of DA in the D4R-/- mice. Baseline extracellular levels of DOPAC and homovanillic acid were also significantly lower in the D4R-/- mice. In vivo chronoamperometric recordings of KCl-evoked release of DA also showed decreased release of DA in the Str and NAc of the D4R-/- mice. These studies demonstrate a role of D4Rs in presynaptic DA regulation and support the hypothesis that alterations in D4Rs may lead to diminished DA function.

Idioma original	English
Páginas (desde-hasta)	306-314
Número de páginas	9
Publicación	Journal of Neuroscience Methods
Volumen	166
N.º	2
DOI	https://doi.org/10.1016/j.jneumeth.2007.03.009
Estado	Published - nov 30 2007

Nota bibliográfica

Funding Information:
These studies were supported by USPHS grants MH070840, P20 RR020171, DA017186, MH066393, and MH067497.

Financiación

These studies were supported by USPHS grants MH070840, P20 RR020171, DA017186, MH066393, and MH067497.

Financiadores	Número del financiador
USPHS	MH070840, MH067497, MH066393, DA017186, P20 RR020171
National Institute of Mental Health	R21MH066393
National Institute of Mental Health

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.jneumeth.2007.03.009

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Thomas, T. C., Kruzich, P. J., Joyce, B. M., Gash, C. R., Suchland, K., Surgener, S. P., Rutherford, E. C., Grandy, D. K., Gerhardt, G. A., & Glaser, P. E. A. (2007). Dopamine D4 receptor knockout mice exhibit neurochemical changes consistent with decreased dopamine release. Journal of Neuroscience Methods, 166(2), 306-314. https://doi.org/10.1016/j.jneumeth.2007.03.009

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title = "Dopamine D4 receptor knockout mice exhibit neurochemical changes consistent with decreased dopamine release",

abstract = "Dopamine D4 receptor (D4R) knockout mice (D4R-/-) provided for unique neurochemical studies designed to understand D4R contributions to dopamine (DA) regulation. In this study, post-mortem brain tissue content of DA did not differ between D4R+/+ and D4R-/- mice in the striatum (Str) or nucleus accumbens core (NAc). However, there was a significant decrease (82\%) in the content of 3,4-dihydoxyphenylacetic acid (DOPAC), a major metabolite of DA, in the NAc of D4R-/- mice. Microdialysis studies performed in a region of brain spanning of the dorsal Str and NAc showed lower baseline levels of DA and a significant reduction in KCl-evoked overflow of DA in the D4R-/- mice. Baseline extracellular levels of DOPAC and homovanillic acid were also significantly lower in the D4R-/- mice. In vivo chronoamperometric recordings of KCl-evoked release of DA also showed decreased release of DA in the Str and NAc of the D4R-/- mice. These studies demonstrate a role of D4Rs in presynaptic DA regulation and support the hypothesis that alterations in D4Rs may lead to diminished DA function.",

keywords = "ADHD, Chronoamperometry, Dopamine, Dopamine receptors, Nucleus accumbens core, Striatum, d-Amphetamine",

author = "Thomas, \{Theresa Currier\} and Kruzich, \{Paul J.\} and Joyce, \{B. Matthew\} and Gash, \{C. R.\} and Katherine Suchland and Surgener, \{Stewart P.\} and Rutherford, \{Erin C.\} and Grandy, \{David K.\} and Gerhardt, \{Greg A.\} and Glaser, \{Paul E.A.\}",

note = "Funding Information: These studies were supported by USPHS grants MH070840, P20 RR020171, DA017186, MH066393, and MH067497. ",

year = "2007",

month = nov,

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doi = "10.1016/j.jneumeth.2007.03.009",

language = "English",

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AU - Thomas, Theresa Currier

AU - Kruzich, Paul J.

AU - Joyce, B. Matthew

AU - Gash, C. R.

AU - Suchland, Katherine

AU - Surgener, Stewart P.

AU - Rutherford, Erin C.

AU - Grandy, David K.

AU - Gerhardt, Greg A.

AU - Glaser, Paul E.A.

N1 - Funding Information: These studies were supported by USPHS grants MH070840, P20 RR020171, DA017186, MH066393, and MH067497.

PY - 2007/11/30

Y1 - 2007/11/30

N2 - Dopamine D4 receptor (D4R) knockout mice (D4R-/-) provided for unique neurochemical studies designed to understand D4R contributions to dopamine (DA) regulation. In this study, post-mortem brain tissue content of DA did not differ between D4R+/+ and D4R-/- mice in the striatum (Str) or nucleus accumbens core (NAc). However, there was a significant decrease (82%) in the content of 3,4-dihydoxyphenylacetic acid (DOPAC), a major metabolite of DA, in the NAc of D4R-/- mice. Microdialysis studies performed in a region of brain spanning of the dorsal Str and NAc showed lower baseline levels of DA and a significant reduction in KCl-evoked overflow of DA in the D4R-/- mice. Baseline extracellular levels of DOPAC and homovanillic acid were also significantly lower in the D4R-/- mice. In vivo chronoamperometric recordings of KCl-evoked release of DA also showed decreased release of DA in the Str and NAc of the D4R-/- mice. These studies demonstrate a role of D4Rs in presynaptic DA regulation and support the hypothesis that alterations in D4Rs may lead to diminished DA function.

AB - Dopamine D4 receptor (D4R) knockout mice (D4R-/-) provided for unique neurochemical studies designed to understand D4R contributions to dopamine (DA) regulation. In this study, post-mortem brain tissue content of DA did not differ between D4R+/+ and D4R-/- mice in the striatum (Str) or nucleus accumbens core (NAc). However, there was a significant decrease (82%) in the content of 3,4-dihydoxyphenylacetic acid (DOPAC), a major metabolite of DA, in the NAc of D4R-/- mice. Microdialysis studies performed in a region of brain spanning of the dorsal Str and NAc showed lower baseline levels of DA and a significant reduction in KCl-evoked overflow of DA in the D4R-/- mice. Baseline extracellular levels of DOPAC and homovanillic acid were also significantly lower in the D4R-/- mice. In vivo chronoamperometric recordings of KCl-evoked release of DA also showed decreased release of DA in the Str and NAc of the D4R-/- mice. These studies demonstrate a role of D4Rs in presynaptic DA regulation and support the hypothesis that alterations in D4Rs may lead to diminished DA function.

KW - ADHD

KW - Chronoamperometry

KW - Dopamine

KW - Dopamine receptors

KW - Nucleus accumbens core

KW - Striatum

KW - d-Amphetamine

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Dopamine D4 receptor knockout mice exhibit neurochemical changes consistent with decreased dopamine release

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

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