Cocaine-responsive gene expression changes in rat hippocampus

W. M. Freeman, K. Brebner, W. J. Lynch, D. J. Robertson, D. C.S. Roberts, Kent Vrana

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Chronic cocaine use is known to elicit changes in the pattern of gene expression within the brain. The hippocampus plays a critical role in learning and memory and may also play a role in mediating behaviors associated with cocaine abuse. To profile the gene expression response of the hippocampus to chronic cocaine treatment, cDNA hybridization arrays were used to illuminate cocaine-regulated genes in rats treated non-contingently with a binge model of cocaine (45 mg/kg/day, i.p.) for 14 days. Validation of mRNA changes illuminated by hybridization array analysis was accomplished by measuring immunoreactive protein (via specific immunoblots). The induction of protein kinase Cα, potassium channel 1.1, and metabotropic glutamate receptor 5 seen by hybridization arrays was confirmed at the level of protein. Immunoblot screening of previously described cocaine-responsive genes demonstrated increased levels of protein tyrosine kinase 2, β-catenin, and protein kinase Cε. While some of these changes exist in previously described cocaine-responsive models, others are novel to any model of cocaine use. The inductions of potassium channel 1.1, protein tyrosine kinase 2 and metabotropic glutamate receptor 5 are novel findings to hippocampal cocaine-responsive gene expression. These proteins have been shown to subserve learning and memory and/or long-term potentiation functions within the hippocampus. Additionally, these genes are known to interact with one another, forming a more complex pattern of gene expression changes. The findings suggest altered expression of genes with a number of different functions in the rat hippocampus after a 'binge' style of non-contingent cocaine administration. These changes in gene expression may play roles in neuronal plasticity and the behavioral phenomena associated with cocaine abuse.

Original languageEnglish (US)
Pages (from-to)371-380
Number of pages10
JournalNeuroscience
Volume108
Issue number3
DOIs
StatePublished - Dec 18 2001

Fingerprint

Cocaine
Hippocampus
Gene Expression
Focal Adhesion Kinase 1
Metabotropic Glutamate 5 Receptor
Cocaine-Related Disorders
Potassium Channels
Protein Kinase C
Learning
Genes
Catenins
Proteins
Neuronal Plasticity
Long-Term Potentiation
Oligonucleotide Array Sequence Analysis
Transcriptome
Messenger RNA
Brain

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Freeman, W. M., Brebner, K., Lynch, W. J., Robertson, D. J., Roberts, D. C. S., & Vrana, K. (2001). Cocaine-responsive gene expression changes in rat hippocampus. Neuroscience, 108(3), 371-380. https://doi.org/10.1016/S0306-4522(01)00432-8
Freeman, W. M. ; Brebner, K. ; Lynch, W. J. ; Robertson, D. J. ; Roberts, D. C.S. ; Vrana, Kent. / Cocaine-responsive gene expression changes in rat hippocampus. In: Neuroscience. 2001 ; Vol. 108, No. 3. pp. 371-380.
@article{0714bc0ff4cc43528369abe27da18696,
title = "Cocaine-responsive gene expression changes in rat hippocampus",
abstract = "Chronic cocaine use is known to elicit changes in the pattern of gene expression within the brain. The hippocampus plays a critical role in learning and memory and may also play a role in mediating behaviors associated with cocaine abuse. To profile the gene expression response of the hippocampus to chronic cocaine treatment, cDNA hybridization arrays were used to illuminate cocaine-regulated genes in rats treated non-contingently with a binge model of cocaine (45 mg/kg/day, i.p.) for 14 days. Validation of mRNA changes illuminated by hybridization array analysis was accomplished by measuring immunoreactive protein (via specific immunoblots). The induction of protein kinase Cα, potassium channel 1.1, and metabotropic glutamate receptor 5 seen by hybridization arrays was confirmed at the level of protein. Immunoblot screening of previously described cocaine-responsive genes demonstrated increased levels of protein tyrosine kinase 2, β-catenin, and protein kinase Cε. While some of these changes exist in previously described cocaine-responsive models, others are novel to any model of cocaine use. The inductions of potassium channel 1.1, protein tyrosine kinase 2 and metabotropic glutamate receptor 5 are novel findings to hippocampal cocaine-responsive gene expression. These proteins have been shown to subserve learning and memory and/or long-term potentiation functions within the hippocampus. Additionally, these genes are known to interact with one another, forming a more complex pattern of gene expression changes. The findings suggest altered expression of genes with a number of different functions in the rat hippocampus after a 'binge' style of non-contingent cocaine administration. These changes in gene expression may play roles in neuronal plasticity and the behavioral phenomena associated with cocaine abuse.",
author = "Freeman, {W. M.} and K. Brebner and Lynch, {W. J.} and Robertson, {D. J.} and Roberts, {D. C.S.} and Kent Vrana",
year = "2001",
month = "12",
day = "18",
doi = "10.1016/S0306-4522(01)00432-8",
language = "English (US)",
volume = "108",
pages = "371--380",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "3",

}

Freeman, WM, Brebner, K, Lynch, WJ, Robertson, DJ, Roberts, DCS & Vrana, K 2001, 'Cocaine-responsive gene expression changes in rat hippocampus', Neuroscience, vol. 108, no. 3, pp. 371-380. https://doi.org/10.1016/S0306-4522(01)00432-8

Cocaine-responsive gene expression changes in rat hippocampus. / Freeman, W. M.; Brebner, K.; Lynch, W. J.; Robertson, D. J.; Roberts, D. C.S.; Vrana, Kent.

In: Neuroscience, Vol. 108, No. 3, 18.12.2001, p. 371-380.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cocaine-responsive gene expression changes in rat hippocampus

AU - Freeman, W. M.

AU - Brebner, K.

AU - Lynch, W. J.

AU - Robertson, D. J.

AU - Roberts, D. C.S.

AU - Vrana, Kent

PY - 2001/12/18

Y1 - 2001/12/18

N2 - Chronic cocaine use is known to elicit changes in the pattern of gene expression within the brain. The hippocampus plays a critical role in learning and memory and may also play a role in mediating behaviors associated with cocaine abuse. To profile the gene expression response of the hippocampus to chronic cocaine treatment, cDNA hybridization arrays were used to illuminate cocaine-regulated genes in rats treated non-contingently with a binge model of cocaine (45 mg/kg/day, i.p.) for 14 days. Validation of mRNA changes illuminated by hybridization array analysis was accomplished by measuring immunoreactive protein (via specific immunoblots). The induction of protein kinase Cα, potassium channel 1.1, and metabotropic glutamate receptor 5 seen by hybridization arrays was confirmed at the level of protein. Immunoblot screening of previously described cocaine-responsive genes demonstrated increased levels of protein tyrosine kinase 2, β-catenin, and protein kinase Cε. While some of these changes exist in previously described cocaine-responsive models, others are novel to any model of cocaine use. The inductions of potassium channel 1.1, protein tyrosine kinase 2 and metabotropic glutamate receptor 5 are novel findings to hippocampal cocaine-responsive gene expression. These proteins have been shown to subserve learning and memory and/or long-term potentiation functions within the hippocampus. Additionally, these genes are known to interact with one another, forming a more complex pattern of gene expression changes. The findings suggest altered expression of genes with a number of different functions in the rat hippocampus after a 'binge' style of non-contingent cocaine administration. These changes in gene expression may play roles in neuronal plasticity and the behavioral phenomena associated with cocaine abuse.

AB - Chronic cocaine use is known to elicit changes in the pattern of gene expression within the brain. The hippocampus plays a critical role in learning and memory and may also play a role in mediating behaviors associated with cocaine abuse. To profile the gene expression response of the hippocampus to chronic cocaine treatment, cDNA hybridization arrays were used to illuminate cocaine-regulated genes in rats treated non-contingently with a binge model of cocaine (45 mg/kg/day, i.p.) for 14 days. Validation of mRNA changes illuminated by hybridization array analysis was accomplished by measuring immunoreactive protein (via specific immunoblots). The induction of protein kinase Cα, potassium channel 1.1, and metabotropic glutamate receptor 5 seen by hybridization arrays was confirmed at the level of protein. Immunoblot screening of previously described cocaine-responsive genes demonstrated increased levels of protein tyrosine kinase 2, β-catenin, and protein kinase Cε. While some of these changes exist in previously described cocaine-responsive models, others are novel to any model of cocaine use. The inductions of potassium channel 1.1, protein tyrosine kinase 2 and metabotropic glutamate receptor 5 are novel findings to hippocampal cocaine-responsive gene expression. These proteins have been shown to subserve learning and memory and/or long-term potentiation functions within the hippocampus. Additionally, these genes are known to interact with one another, forming a more complex pattern of gene expression changes. The findings suggest altered expression of genes with a number of different functions in the rat hippocampus after a 'binge' style of non-contingent cocaine administration. These changes in gene expression may play roles in neuronal plasticity and the behavioral phenomena associated with cocaine abuse.

UR - http://www.scopus.com/inward/record.url?scp=0035910162&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035910162&partnerID=8YFLogxK

U2 - 10.1016/S0306-4522(01)00432-8

DO - 10.1016/S0306-4522(01)00432-8

M3 - Article

VL - 108

SP - 371

EP - 380

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 3

ER -

Freeman WM, Brebner K, Lynch WJ, Robertson DJ, Roberts DCS, Vrana K. Cocaine-responsive gene expression changes in rat hippocampus. Neuroscience. 2001 Dec 18;108(3):371-380. https://doi.org/10.1016/S0306-4522(01)00432-8