Enhanced CREB phosphorylation and changes in c-Fos and FRA expression in striatum accompany amphetamine sensitization

Turgeon, Sarah M.; Pollack, Alexia E.; Fink, J. Stephen

doi:10.1016/s0006-8993(96)01316-9

Cited by 119 publications

(84 citation statements)

References 41 publications

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“…Previous reports demonstrate that chronic administration of a psychostimulant (e.g., cocaine or amphetamine) up-regulates the cAMP pathway, which leads to activation of CRE/CREB-mediated transcription in nucleus accumbens and dorsal striatum (Terwilliger et al, 1991;Konradi et al, 1994;Cole et al, 1995;Hyman, 1996;Unterwald et al, 1996;Nestler, 1997;Nestler and Aghajanian, 1997;Turgeon et al, 1997). In addition, dynorphin has been shown to be a target of CREB-mediated transactivation in these regions after chronic cocaine or amphetamine treatment (Hurd et al, 1992;Daunais et al, 1993;Spangler et al, 1993;Cole et al, 1995;Carlezon et al, 1998).…”

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confidence: 99%

Inducible and Brain Region-Specific CREB Transgenic Mice

et al. 2002

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To investigate the role of cAMP response element-binding protein (CREB) in the adaptive responses to psychotropic drugs, we have developed inducible, brain region-specific CREB transgenic mice using the tetracycline-regulated gene expression system. The tetracycline transactivator (tTA) was placed under the control of 1.8-kilobase neuron-specific enolase (NSE) promoter for this purpose. Different patterns of CREB overexpression were found in striatum, nucleus accumbens, and cingulate cortex in different lines of bitransgenic mice, and CREB expression was blocked by addition of doxycycline, an analog of tetracycline. Overexpression of CREB influenced the expression of other members of the CREB/ATF family of transcription factors, consistent with previous reports. In addition, psychostimulant induction of dynorphin, a neuropeptide regulated by drugs of abuse, was up-regulated in striatum. Finally, there was a significant reduction in cocaine-induced locomotor activity in the CREB bitransgenic mice. These results are consistent with a role for CREB in mediating adaptive changes that occur in response to drugs of abuse.

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confidence: 99%

Inducible and Brain Region-Specific CREB Transgenic Mice

et al. 2002

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“…Activation (accomplished via phosphorylation) of a Ca 2+ /cAMP response element-binding protein (CREB) (Montminy and Bilezikjian, 1987;Gonzalez et al, 1989) initiates expression of genes whose protein products are regulators of transmitter systems engaged by abused drugs (Chrivia et al, 1993). pCREB and CREB levels are altered in various brain regions following exposure to drugs of abuse (Guitart et al, 1992;Turgeon et al, 1997). With regard to opiates, following 24 h withdrawal from 5 days of continuous morphine exposure (75 mg pellet s.c.), levels of CREB-like immunoreactivity are decreased in the NAc (Widnell et al, 1996).…”

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confidence: 99%

Changes in Accumbal and Pallidal pCREB and ΔFosB in Morphine-Sensitized Rats: Correlations with Receptor-Evoked Electrophysiological Measures in the Ventral Pallidum

McDaid

Dallimore

Mackie

et al. 2005

Neuropsychopharmacol

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Activation of μ-opioid receptors in the ventral pallidum (VP) is important for the induction of behavioral sensitization to morphine in rats. The present study was designed to ascertain if neurons within the VP demonstrate sensitization at a time when morphine-induced behavioral sensitization occurred (ie 3 or 14 days after five once-daily injections of 10 mg/kg i.p. morphine) in rats. Western blotting was used to evaluate transcription factors altered by opiates, CREB and ΔFosB. CREB levels did not change in the VP, but there was a significant decrease in levels of its active, phosphorylated form (pCREB) at both 3-and 14-days withdrawal. ΔFosB levels were elevated following a 3-day withdrawal, but returned to normal by 14 days. This profile also was obtained from nucleus accumbens tissue. In a separate group of similarly treated rats, in vivo electrophysiological recordings of VP neuronal responses to microiontophoretically applied ligands were carried out after 14-days withdrawal. The firing rate effects of local applications of morphine were diminished in rats withdrawn from i.p. morphine. Repeated i.p. morphine did not alter GABA-mediated suppression of firing, or the rate enhancing effects of the D1 dopamine receptor agonist SKF82958 or glutamate. However, VP neurons from rats withdrawn from repeated i.p. morphine showed a higher propensity to enter a state of depolarization inactivation to locally applied glutamate. Overall, these findings reveal that decreased pCREB in brain regions such as the VP accompanies persistent behavioral sensitization to morphine and that this biochemical alteration may influence the excitability of neurons in this brain region.

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“…The cAMP response element (CRE)-binding protein, CREB, is a constitutively expressed transcription factor activated by phosphorylation through the cAMP pathway and other intracellular signaling cascades (1). Within the central nervous system, CREB has been associated with learning and memory (2)(3)(4)(5)(6), as well as with molecular and behavioral changes induced by antidepressants (7,8) and drugs of abuse (9)(10)(11)(12)(13)(14)(15). In these latter cases, changes in second messenger pathways activating CREB (7,9), changes in CREB levels (12), and changes in CRE-mediated transcription (8,15) have been observed in several discrete brain areas.…”

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CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli

Barrot

Olivier

Perrotti

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

448

428

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The transcription factor cAMP response element (CRE)-binding protein (CREB) has been shown to regulate neural plasticity. Drugs of abuse activate CREB in the nucleus accumbens, an important part of the brain's reward pathways, and local manipulations of CREB activity have been shown to affect cocaine reward, suggesting an active role of CREB in adaptive processes that follow exposure to drugs of abuse. Using CRE-LacZ reporter mice, we show that not only rewarding stimuli such as morphine, but also aversive stimuli such as stress, activate CRE-mediated transcription in the nucleus accumbens shell. Using viral-mediated gene transfer to locally alter the activity of CREB, we show that this manipulation affects morphine reward, as well as the preference for sucrose, a more natural reward. We then show that local changes in CREB activity induce a more general syndrome, by altering reactions to anxiogenic, aversive, and nociceptive stimuli as well. Increased CREB activity in the nucleus accumbens shell decreases an animal's responses to each of these stimuli, whereas decreased CREB activity induces an opposite phenotype. These results show that environmental stimuli regulate CRE-mediated transcription within the nucleus accumbens shell, and that changes in CREB activity within this brain area subsequently alter gating between emotional stimuli and their behavioral responses. This control appears to be independent of the intrinsic appetitive or aversive value of the stimulus. The potential relevance of these data to addiction and mood disorders is discussed.T ranscription factors, by regulating protein expression, participate in neural plasticity and adaptation. Stimuli that change transcriptional activity in a brain structure may alter over time the way information is processed by that structure. At more integrated levels, this plasticity can lead to changes in the interaction between an individual and its environment. Examples include learning processes, and changes in perception, interpretation, and behavioral responses to environmental stimuli. The cAMP response element (CRE)-binding protein, CREB, is a constitutively expressed transcription factor activated by phosphorylation through the cAMP pathway and other intracellular signaling cascades (1). Within the central nervous system, CREB has been associated with learning and memory (2-6), as well as with molecular and behavioral changes induced by antidepressants (7, 8) and drugs of abuse (9-15). In these latter cases, changes in second messenger pathways activating CREB (7, 9), changes in CREB levels (12), and changes in CRE-mediated transcription (8, 15) have been observed in several discrete brain areas.The nucleus accumbens, a forebrain structure critical for reward and motivation (16-23), has a key role in reinforcing properties of drugs of abuse (12,(17)(18)(19)(20)(21). Chronic exposure to cocaine or to several other drugs of abuse increases cAMP levels and cAMP-dependent protein kinase (PKA) activity in the nucleus accumbens (9, 12). These adaptations cause...

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Enhanced CREB phosphorylation and changes in c-Fos and FRA expression in striatum accompany amphetamine sensitization

Cited by 119 publications

References 41 publications

Inducible and Brain Region-Specific CREB Transgenic Mice

Inducible and Brain Region-Specific CREB Transgenic Mice

Changes in Accumbal and Pallidal pCREB and ΔFosB in Morphine-Sensitized Rats: Correlations with Receptor-Evoked Electrophysiological Measures in the Ventral Pallidum

CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli

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