NMDA and D1 receptors mediate induction of c-fos and junB genes in striatum following morphine administration: implications for studies of memory

Frank R Sharp, Jialing Liu, Jeremy Nickolenko, Bruno Bontempi

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The c-fos and junB immediate early genes (IEGs) were induced in neurons of the medial and ventral striatum following administration of morphine. The striatal induction of c-fos and junB mRNA and Fos protein was blocked by naloxone, the D1 dopamine (DA) receptor antagonists, SCH23390 and SCH39166, and the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, MK801. SCH23390 and MK801 did not block morphine induction of c-fos and junB in septum. Since the pattern of the morphine induction of c-fos and junB in striatum and nucleus accumbens was similar to that observed with cocaine and amphetamine [2,18,45,51], these data support current concepts that limbic striatum and nucleus accumbens are among the brain regions that mediate drug abuse [9,10,23,27,49]. If it is true that D1 receptors activate the CRE (cyclase response element) and NMDA receptors activate the SRE (serum response element) in the c-fos promoter [1], then this data suggests that serial activation of μ opiate, NMDA and D1 receptors on different neurons is required to induced Fos in striatal neurons with D1 receptors. Moreover, concurrent activation of NMDA and D1 receptors is required for Fos induction in striatal neurons. The Fos induced by this simultaneous activation of NMDA and D1 receptors should lead to long-term changes of gene expression that might also be involved in changes of brain circuits that could form the basis for 'memories' relating to prior exposure to addictive drugs.

Original languageEnglish (US)
Pages (from-to)225-230
Number of pages6
JournalBehavioural Brain Research
Volume66
Issue number1-2
DOIs
StatePublished - Jan 23 1995
Externally publishedYes

Keywords

  • Addiction
  • c-fos
  • Dopamine receptor
  • Glutamate
  • Immediate early gene
  • junB
  • Memory
  • Morphine
  • NMDA receptor
  • Striatum
  • Transcription factor

ASJC Scopus subject areas

  • Behavioral Neuroscience

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