Induction of inducible cAMP early repressor expression in nucleus accumbens by stress or amphetamine increases behavioral responses to emotional stimuli

Thomas Green, Imran N. Alibhai, Jonathan Hommel, Ralph J. DiLeone, Arvind Kumar, David E. Theobald, Rachael L. Neve, Eric J. Nestler

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Previous research has shown that cAMP response element (CRE)-mediated transcription is activated in the nucleus accumbens, a major brain reward region, by a variety of environmental stimuli and contributes to neuroadaptations to these stimuli. CRE-binding protein (CREB) is the most studied activator of CRE transcription and has been implicated in this brain region as a gating mechanism for behavioral responses to emotional stimuli. Little attention, however, has been given to naturally occurring inhibitors of CRE-mediated transcription, such as the inducible cAMP early repressor (ICER), an inhibitory product of the CRE modulator gene. In the present study, we investigated the extent to which ICER is induced in the nucleus accumbens by two types of environmental stimuli, stress and amphetamine, and characterized how induction of ICER in this region affects complex behavior. We show that stress and amphetamine each induces ICER expression and that overexpression of ICER in the nucleus accumbens, using viral-mediated gene transfer, increases behavioral responses to both rewarding and aversive emotional stimuli. For example, ICER overexpression increases sensitivity to amphetamine-stimulated locomotor activity as well as to natural rewards such as sucrose and social grooming. However, ICER overexpression also increases measures of anxiety in the elevated plus maze and neophobia to novel tastes. Finally, ICER produces an antidepressant-like effect in the forced swim test, further indication of an enhanced active response to stress. These results suggest that ICER is an important mechanism for modulating CRE-mediated transcription in the nucleus accumbens.

Original languageEnglish (US)
Pages (from-to)8235-8242
Number of pages8
JournalJournal of Neuroscience
Volume26
Issue number32
DOIs
StatePublished - Aug 9 2006
Externally publishedYes

Fingerprint

Nucleus Accumbens
Response Elements
Amphetamine
Reward
Cyclic AMP Response Element-Binding Protein
Grooming
Viral Genes
Brain
Locomotion
Antidepressive Agents
Sucrose
Anxiety
Research
Genes

Keywords

  • Addiction
  • Anxiety
  • Cocaine
  • CREB
  • CREM
  • Depression
  • Drugs of abuse
  • Stimulants
  • Striatum
  • Sucrose preference

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Induction of inducible cAMP early repressor expression in nucleus accumbens by stress or amphetamine increases behavioral responses to emotional stimuli. / Green, Thomas; Alibhai, Imran N.; Hommel, Jonathan; DiLeone, Ralph J.; Kumar, Arvind; Theobald, David E.; Neve, Rachael L.; Nestler, Eric J.

In: Journal of Neuroscience, Vol. 26, No. 32, 09.08.2006, p. 8235-8242.

Research output: Contribution to journalArticle

Green, Thomas ; Alibhai, Imran N. ; Hommel, Jonathan ; DiLeone, Ralph J. ; Kumar, Arvind ; Theobald, David E. ; Neve, Rachael L. ; Nestler, Eric J. / Induction of inducible cAMP early repressor expression in nucleus accumbens by stress or amphetamine increases behavioral responses to emotional stimuli. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 32. pp. 8235-8242.
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