Zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine
Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically r...
Ausführliche Beschreibung
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| Autor*in: |
Webb, Katharine J [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2009 |
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| Anmerkung: |
© Webb et al.; licensee BioMed Central Ltd. 2009. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( |
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| Übergeordnetes Werk: |
Enthalten in: Genome biology - London : BioMed Central, 2000, 10(2009), 7 vom: 31. Juli |
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| Übergeordnetes Werk: |
volume:10 ; year:2009 ; number:7 ; day:31 ; month:07 |
| Links: |
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| DOI / URN: |
10.1186/gb-2009-10-7-r81 |
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SPR030006538 |
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| 520 | |a Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (naddne3256), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. Results Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes. Conclusions Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction. | ||
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10.1186/gb-2009-10-7-r81 doi (DE-627)SPR030006538 (SPR)gb-2009-10-7-r81-e DE-627 ger DE-627 rakwb eng Webb, Katharine J verfasserin aut Zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Webb et al.; licensee BioMed Central Ltd. 2009. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (naddne3256), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. Results Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes. Conclusions Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction. Cocaine (dpeaa)DE-He213 Amphetamine (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Conditioned Place Preference (dpeaa)DE-He213 Place Preference (dpeaa)DE-He213 Norton, William HJ aut Trümbach, Dietrich aut Meijer, Annemarie H aut Ninkovic, Jovica aut Topp, Stefanie aut Heck, Daniel aut Marr, Carsten aut Wurst, Wolfgang aut Theis, Fabian J aut Spaink, Herman P aut Bally-Cuif, Laure aut Enthalten in Genome biology London : BioMed Central, 2000 10(2009), 7 vom: 31. Juli (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:10 year:2009 number:7 day:31 month:07 https://dx.doi.org/10.1186/gb-2009-10-7-r81 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2009 7 31 07 |
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10.1186/gb-2009-10-7-r81 doi (DE-627)SPR030006538 (SPR)gb-2009-10-7-r81-e DE-627 ger DE-627 rakwb eng Webb, Katharine J verfasserin aut Zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Webb et al.; licensee BioMed Central Ltd. 2009. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (naddne3256), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. Results Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes. Conclusions Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction. Cocaine (dpeaa)DE-He213 Amphetamine (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Conditioned Place Preference (dpeaa)DE-He213 Place Preference (dpeaa)DE-He213 Norton, William HJ aut Trümbach, Dietrich aut Meijer, Annemarie H aut Ninkovic, Jovica aut Topp, Stefanie aut Heck, Daniel aut Marr, Carsten aut Wurst, Wolfgang aut Theis, Fabian J aut Spaink, Herman P aut Bally-Cuif, Laure aut Enthalten in Genome biology London : BioMed Central, 2000 10(2009), 7 vom: 31. Juli (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:10 year:2009 number:7 day:31 month:07 https://dx.doi.org/10.1186/gb-2009-10-7-r81 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2009 7 31 07 |
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10.1186/gb-2009-10-7-r81 doi (DE-627)SPR030006538 (SPR)gb-2009-10-7-r81-e DE-627 ger DE-627 rakwb eng Webb, Katharine J verfasserin aut Zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Webb et al.; licensee BioMed Central Ltd. 2009. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (naddne3256), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. Results Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes. Conclusions Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction. Cocaine (dpeaa)DE-He213 Amphetamine (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Conditioned Place Preference (dpeaa)DE-He213 Place Preference (dpeaa)DE-He213 Norton, William HJ aut Trümbach, Dietrich aut Meijer, Annemarie H aut Ninkovic, Jovica aut Topp, Stefanie aut Heck, Daniel aut Marr, Carsten aut Wurst, Wolfgang aut Theis, Fabian J aut Spaink, Herman P aut Bally-Cuif, Laure aut Enthalten in Genome biology London : BioMed Central, 2000 10(2009), 7 vom: 31. Juli (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:10 year:2009 number:7 day:31 month:07 https://dx.doi.org/10.1186/gb-2009-10-7-r81 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2009 7 31 07 |
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10.1186/gb-2009-10-7-r81 doi (DE-627)SPR030006538 (SPR)gb-2009-10-7-r81-e DE-627 ger DE-627 rakwb eng Webb, Katharine J verfasserin aut Zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Webb et al.; licensee BioMed Central Ltd. 2009. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (naddne3256), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. Results Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes. Conclusions Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction. Cocaine (dpeaa)DE-He213 Amphetamine (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Conditioned Place Preference (dpeaa)DE-He213 Place Preference (dpeaa)DE-He213 Norton, William HJ aut Trümbach, Dietrich aut Meijer, Annemarie H aut Ninkovic, Jovica aut Topp, Stefanie aut Heck, Daniel aut Marr, Carsten aut Wurst, Wolfgang aut Theis, Fabian J aut Spaink, Herman P aut Bally-Cuif, Laure aut Enthalten in Genome biology London : BioMed Central, 2000 10(2009), 7 vom: 31. Juli (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:10 year:2009 number:7 day:31 month:07 https://dx.doi.org/10.1186/gb-2009-10-7-r81 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2009 7 31 07 |
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10.1186/gb-2009-10-7-r81 doi (DE-627)SPR030006538 (SPR)gb-2009-10-7-r81-e DE-627 ger DE-627 rakwb eng Webb, Katharine J verfasserin aut Zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Webb et al.; licensee BioMed Central Ltd. 2009. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (naddne3256), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. Results Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes. Conclusions Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction. Cocaine (dpeaa)DE-He213 Amphetamine (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Conditioned Place Preference (dpeaa)DE-He213 Place Preference (dpeaa)DE-He213 Norton, William HJ aut Trümbach, Dietrich aut Meijer, Annemarie H aut Ninkovic, Jovica aut Topp, Stefanie aut Heck, Daniel aut Marr, Carsten aut Wurst, Wolfgang aut Theis, Fabian J aut Spaink, Herman P aut Bally-Cuif, Laure aut Enthalten in Genome biology London : BioMed Central, 2000 10(2009), 7 vom: 31. Juli (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:10 year:2009 number:7 day:31 month:07 https://dx.doi.org/10.1186/gb-2009-10-7-r81 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2009 7 31 07 |
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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (naddne3256), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. 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Webb, Katharine J Norton, William HJ Trümbach, Dietrich Meijer, Annemarie H Ninkovic, Jovica Topp, Stefanie Heck, Daniel Marr, Carsten Wurst, Wolfgang Theis, Fabian J Spaink, Herman P Bally-Cuif, Laure |
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zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine |
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Zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine |
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Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (naddne3256), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. Results Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes. Conclusions Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction. © Webb et al.; licensee BioMed Central Ltd. 2009. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( |
| abstractGer |
Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (naddne3256), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. Results Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes. Conclusions Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction. © Webb et al.; licensee BioMed Central Ltd. 2009. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( |
| abstract_unstemmed |
Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (naddne3256), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. Results Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes. Conclusions Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction. © Webb et al.; licensee BioMed Central Ltd. 2009. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( |
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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (naddne3256), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. Results Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes. Conclusions Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cocaine</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Amphetamine</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Additional Data File</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Conditioned Place Preference</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Place Preference</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Norton, William HJ</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Trümbach, Dietrich</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Meijer, Annemarie H</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ninkovic, Jovica</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Topp, Stefanie</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Heck, Daniel</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Marr, Carsten</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wurst, Wolfgang</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Theis, Fabian J</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Spaink, Herman P</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Bally-Cuif, Laure</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Genome biology</subfield><subfield code="d">London : BioMed Central, 2000</subfield><subfield code="g">10(2009), 7 vom: 31. 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