mRNAs for clozapine-sensitive receptors co-localize in rat prefrontal cortex neurons

Alexander Vysokanov; Jorge Flores-Hernandez; D. James Surmeier

doi:10.1016/S0304-3940(98)00882-9

mRNAs for clozapine-sensitive receptors co-localize in rat prefrontal cortex neurons

Alexander Vysokanov, Jorge Flores-Hernandez, D. James Surmeier^*

^*Corresponding author for this work

Physiology

Research output: Contribution to journal › Article › peer-review

50 Scopus citations

Abstract

The clinical efficacy of clozapine in treating schizophrenia may Stem from its lack of receptor selectivity. If true, several clozapine-sensitive receptors may be co-expressed by neurons dysfunctional in schizophrenia. To test this hypothesis, neurons from the rat medial prefrontal cortex were acutely isolated and subjected to single cell RT-PCR analysis. The co- ordinated expression of five clozapine-sensitive receptors (D₄, ml, 5- HT(2a), 5-HT(2c), 5-HT₇) was examined in interneurons and pyramidal neurons. Profiling of GABAergic interneurons commonly revealed the co-expression of two or more clozapine-sensitive receptor mRNAs. Although co-expression of these receptors was less extensive in pyramidal neurons, it was also commonly found. These results suggest that clozapine's therapeutic effects may be mediated by antagonism of dopaminergic, cholinergic and serotoninergic signaling pathways at the single cell level.

Original language	English (US)
Pages (from-to)	179-182
Number of pages	4
Journal	Neuroscience Letters
Volume	258
Issue number	3
DOIs	https://doi.org/10.1016/S0304-3940(98)00882-9
State	Published - Dec 24 1998

Keywords

Acetylcholine
Dopamine
GABA
Interneurons
Prefrontal cortex
Pyramidal neurons
Schizophrenia
Serotonin
Single cell RT-PCR

ASJC Scopus subject areas

Neuroscience(all)

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title = "mRNAs for clozapine-sensitive receptors co-localize in rat prefrontal cortex neurons",

abstract = "The clinical efficacy of clozapine in treating schizophrenia may Stem from its lack of receptor selectivity. If true, several clozapine-sensitive receptors may be co-expressed by neurons dysfunctional in schizophrenia. To test this hypothesis, neurons from the rat medial prefrontal cortex were acutely isolated and subjected to single cell RT-PCR analysis. The co- ordinated expression of five clozapine-sensitive receptors (D4, ml, 5- HT(2a), 5-HT(2c), 5-HT7) was examined in interneurons and pyramidal neurons. Profiling of GABAergic interneurons commonly revealed the co-expression of two or more clozapine-sensitive receptor mRNAs. Although co-expression of these receptors was less extensive in pyramidal neurons, it was also commonly found. These results suggest that clozapine's therapeutic effects may be mediated by antagonism of dopaminergic, cholinergic and serotoninergic signaling pathways at the single cell level.",

keywords = "Acetylcholine, Dopamine, GABA, Interneurons, Prefrontal cortex, Pyramidal neurons, Schizophrenia, Serotonin, Single cell RT-PCR",

author = "Alexander Vysokanov and Jorge Flores-Hernandez and Surmeier, {D. James}",

note = "Funding Information: This work was supported by an Established Investigator award from NARSAD to D.J.S. Much of this work was performed at the University of Tennessee, Memphis, TN. We wish to thank Tatiana Tkatch and Gytis Baranauskas for careful reading of the manuscript and helpful discussions.",

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doi = "10.1016/S0304-3940(98)00882-9",

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AU - Surmeier, D. James

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PY - 1998/12/24

Y1 - 1998/12/24

N2 - The clinical efficacy of clozapine in treating schizophrenia may Stem from its lack of receptor selectivity. If true, several clozapine-sensitive receptors may be co-expressed by neurons dysfunctional in schizophrenia. To test this hypothesis, neurons from the rat medial prefrontal cortex were acutely isolated and subjected to single cell RT-PCR analysis. The co- ordinated expression of five clozapine-sensitive receptors (D4, ml, 5- HT(2a), 5-HT(2c), 5-HT7) was examined in interneurons and pyramidal neurons. Profiling of GABAergic interneurons commonly revealed the co-expression of two or more clozapine-sensitive receptor mRNAs. Although co-expression of these receptors was less extensive in pyramidal neurons, it was also commonly found. These results suggest that clozapine's therapeutic effects may be mediated by antagonism of dopaminergic, cholinergic and serotoninergic signaling pathways at the single cell level.

AB - The clinical efficacy of clozapine in treating schizophrenia may Stem from its lack of receptor selectivity. If true, several clozapine-sensitive receptors may be co-expressed by neurons dysfunctional in schizophrenia. To test this hypothesis, neurons from the rat medial prefrontal cortex were acutely isolated and subjected to single cell RT-PCR analysis. The co- ordinated expression of five clozapine-sensitive receptors (D4, ml, 5- HT(2a), 5-HT(2c), 5-HT7) was examined in interneurons and pyramidal neurons. Profiling of GABAergic interneurons commonly revealed the co-expression of two or more clozapine-sensitive receptor mRNAs. Although co-expression of these receptors was less extensive in pyramidal neurons, it was also commonly found. These results suggest that clozapine's therapeutic effects may be mediated by antagonism of dopaminergic, cholinergic and serotoninergic signaling pathways at the single cell level.

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KW - Serotonin

KW - Single cell RT-PCR

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mRNAs for clozapine-sensitive receptors co-localize in rat prefrontal cortex neurons

Abstract

Keywords

ASJC Scopus subject areas

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