Changes in rat frontal cortex gene expression following chronic cocaine

Freeman, Willard M.; Brebner, Karen; Lynch, Wendy J.; Patel, Kruti M.; Robertson, Daniel J.; Roberts, David C. S.; Vrana, Kent E.

doi:10.1016/s0169-328x(02)00197-3

Cited by 54 publications

(36 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, we found increases in Arc protein in the mPFC after chronic noncontingent (Freeman et al, 2002a), but not self-administered, cocaine (Freeman et al, 2002b). Recently, a temporal analysis of Arc protein levels was examined after noncontingent cocaine administration (Fumagalli et al, 2006).…”

Section: Discussionmentioning

confidence: 59%

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

Freeman

Patel

Brucklacher

et al. 2007

Neuropsychopharmacol

Self Cite

110

126

View full text Add to dashboard Cite

Cocaine-responsive gene expression changes have been described after either no drug abstinence or short periods of abstinence. Little data exist on the persistence of these changes after long-term abstinence. Previously, we reported that after discrete-trial cocaine selfadministration and 10 days of forced abstinence, incubation of cocaine reinforcement was observable by a progressive ratio schedule. The present study used rat discrete-trial cocaine self-administration and long-term forced abstinence to examine extinction responding, mRNA abundance of known cocaine-responsive genes, and chromatin remodeling. At 30 and 100 days of abstinence, extinction responding increased compared to 3-day abstinent rats. Decreases in both medial prefrontal cortex (mPFC) and nucleus accumbens cfos, Nr4a1, Arc, and EGR1 mRNA were observed, and in most cases persisted, for 100 days of abstinence. The signaling peptides CART and neuropeptide Y (NPY) transiently increased in the mPFC, but returned to baseline levels following 10 days of abstinence. To investigate a potential regulatory mechanism for these persistent mRNA changes, levels of histone H3 acetylation at promoters for genes with altered mRNA expression were examined. In the mPFC, histone H3 acetylation decreased after 1 and 10 days of abstinence at the promoter for EGR1. H3 acetylation increased for NPY after 1 day of abstinence and returned to control levels by 10 days of abstinence.Behaviorally, these results demonstrate incubation after discrete-trial cocaine self-administration and prolonged forced abstinence. This incubation is accompanied by changes in gene expression that persist long after cessation of drug administration and may be regulated by chromatin remodeling.

show abstract

Section: Discussionmentioning

confidence: 59%

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

Freeman

Patel

Brucklacher

et al. 2007

Neuropsychopharmacol

Self Cite

110

126

View full text Add to dashboard Cite

show abstract

“…Chronic morphine produced a significant increase in the mRNA and protein levels of Arc in rat striatum. The modulation of this protein in different rat brain structures by several drugs of abuse has been previously described (Ammon et al, 2003;Fosnaugh et al, 1995;Freeman et al, 2002;Kodama et al, 1998;Tan et al, 2000). The exact function of Arc is unknown but its induction and localization in dendrites and soma (Steward and Worley, 2001;Wallace et al, 1998) led to the hypothesis of its involvement in cytoskeletal rearrangements during the process of synaptic plasticity (Lyford et al, 1995).…”

Section: Discussionmentioning

confidence: 94%

Cytoskeletal Genes Regulation by Chronic Morphine Treatment in Rat Striatum

Marie-Claire

Courtin

Roques

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

It has been previously suggested that morphine can regulate the expression and function of some proteins of the cytoskeleton. In the present study, we used real-time quantitative polymerase chain reaction to examine the effects of chronic morphine administration, in rat striatum, on 14 proteins involved in microtubule polymerization and stabilization, intracellular trafficking, and serving as markers of neuronal growth and degeneration. Chronic morphine treatment led to modulation of the mRNA level of seven of the 14 genes tested. Glial fibrillary acidic protein (Gfap) and activity-regulated cytoskeleton-associated protein (Arc) mRNA were upregulated, while growth associated protein (Gap43), clathrin heavy chain (Cltc), a-tubulin, Tau, and stathmin were downregulated. In order to determine if the regulation of an mRNA correlates with a modulation of the expression of the corresponding protein, immunoblot analyses were performed. With the exception of Gap43, the levels of Cltc, Gfap, Tau, stathmin, and a-tubulin proteins were found to be in good agreement with those from mRNA quantification. These results demonstrate that neuroadaptation to chronic morphine administration in rat striatum implies modifications of the expression pattern of several genes and proteins of the cytoskeleton and cytoskeletonassociated components.

show abstract

“…Animal model studies have shown that appropriate Arc expression is essential for LTP and long-term memory formation (Guzowski et al, 2000). Besides being linked to drug abuse and sleep disruption (Cirelli and Tononi, 2000;Freeman et al, 2002), the ectopic and aberrant expression of Arc has been predicted to cause failure of long-term memory formation (Guzowski, 2002). .…”

Section: Clusters Of Addl Binding Sites Are Coincident With Synapsesmentioning

confidence: 99%

Synaptic Targeting by Alzheimer's-Related Amyloid β Oligomers

Lacor

Buniel²,

Chang³

et al. 2004

J. Neurosci.

903

805

View full text Add to dashboard Cite

The cognitive hallmark of early Alzheimer's disease (AD) is an extraordinary inability to form new memories. For many years, this dementia was attributed to nerve-cell death induced by deposits of fibrillar amyloid ␤ (A␤). A newer hypothesis has emerged, however, in which early memory loss is considered a synapse failure caused by soluble A␤ oligomers. Such oligomers rapidly block long-term potentiation, a classic experimental paradigm for synaptic plasticity, and they are strikingly elevated in AD brain tissue and transgenicmouse AD models. The current work characterizes the manner in which A␤ oligomers attack neurons. Antibodies raised against synthetic oligomers applied to AD brain sections were found to give diffuse stain around neuronal cell bodies, suggestive of a dendritic pattern, whereas soluble brain extracts showed robust AD-dependent reactivity in dot immunoblots. Antigens in unfractionated AD extracts attached with specificity to cultured rat hippocampal neurons, binding within dendritic arbors at discrete puncta. Crude fractionation showed ligand size to be between 10 and 100 kDa. Synthetic A␤ oligomers of the same size gave identical punctate binding, which was highly selective for particular neurons. Image analysis by confocal double-label immunofluorescence established that Ͼ90% of the punctate oligomer binding sites colocalized with the synaptic marker PSD-95 (postsynaptic density protein 95). Synaptic binding was accompanied by ectopic induction of Arc, a synaptic immediate-early gene, the overexpression of which has been linked to dysfunctional learning. Results suggest the hypothesis that targeting and functional disruption of particular synapses by A␤ oligomers may provide a molecular basis for the specific loss of memory function in early AD.

show abstract

Changes in rat frontal cortex gene expression following chronic cocaine

Cited by 54 publications

References 45 publications

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

Cytoskeletal Genes Regulation by Chronic Morphine Treatment in Rat Striatum

Synaptic Targeting by Alzheimer's-Related Amyloid β Oligomers

Contact Info

Product

Resources

About