Alterations in PKCγ in the mouse hippocampus after prenatal exposure to heroin: A link from cell signaling to behavioral outcome

Halit Shahak, Theodore A. Slotkin, Joseph Yanai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Administration of heroin to pregnant mice evokes neurochemical and behavioral deficits consequent to disruption of septohippocampal cholinergic innervation, notably involving desensitization of the ability of cholinergic receptors to activate PKC activity. The present study further evaluates whether desensitization occurs specifically for the PKCγ isoform, the behaviorally relevant subtype, as compared to PKCα. Mice were exposed transplacentally to heroin on gestational days (GD) 9-18 via s.c. maternal injections (10 mg/kg per day). In young adulthood (50 days old), control offspring showed an increase in hippocampal cell membrane PKCγ after incubation with the muscarinic cholinergic receptor agonist, carbachol, indicative of translocation from the cytosol. Prenatal exposure to heroin eliminated this response, whereas basal PKCγ levels were unchanged. In contrast, PKCα, which is not related to heroin-induced behavioral deficits, did not show a loss of response. The present findings strongly point to abnormalities in the responsiveness of PKCγ as a mechanism underlying the neurobehavioral teratogenicity of heroin.

Original languageEnglish
Pages (from-to)117-125
Number of pages9
JournalDevelopmental Brain Research
Volume140
Issue number1
DOIs
StatePublished - 13 Jan 2003

Keywords

  • Carbachol
  • Heroin
  • Hippocampus
  • Mouse
  • PKCα
  • PKCγ
  • Prenatal exposure

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