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Alterations in PKCgamma in the mouse hippocampus after prenatal exposure to heroin: a link from cell signaling to behavioral outcome.

Publication ,  Journal Article
Shahak, H; Slotkin, TA; Yanai, J
Published in: Brain Res Dev Brain Res
January 10, 2003

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 PKCgamma isoform, the behaviorally relevant subtype, as compared to PKCalpha. 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 PKCgamma after incubation with the muscarinic cholinergic receptor agonist, carbachol, indicative of translocation from the cytosol. Prenatal exposure to heroin eliminated this response, whereas basal PKCgamma levels were unchanged. In contrast, PKCalpha, 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 PKCgamma as a mechanism underlying the neurobehavioral teratogenicity of heroin.

Duke Scholars

Published In

Brain Res Dev Brain Res

DOI

ISSN

0165-3806

Publication Date

January 10, 2003

Volume

140

Issue

1

Start / End Page

117 / 125

Location

Netherlands

Related Subject Headings

  • Signal Transduction
  • Reflex, Startle
  • Reflex
  • Protein Kinase C
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Posture
  • Neurology & Neurosurgery
  • Models, Animal
  • Mice
 

Citation

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Shahak, H., Slotkin, T. A., & Yanai, J. (2003). Alterations in PKCgamma in the mouse hippocampus after prenatal exposure to heroin: a link from cell signaling to behavioral outcome. Brain Res Dev Brain Res, 140(1), 117–125. https://doi.org/10.1016/s0165-3806(02)00607-7
Shahak, Halit, Theodore A. Slotkin, and Joseph Yanai. “Alterations in PKCgamma in the mouse hippocampus after prenatal exposure to heroin: a link from cell signaling to behavioral outcome.Brain Res Dev Brain Res 140, no. 1 (January 10, 2003): 117–25. https://doi.org/10.1016/s0165-3806(02)00607-7.
Shahak, Halit, et al. “Alterations in PKCgamma in the mouse hippocampus after prenatal exposure to heroin: a link from cell signaling to behavioral outcome.Brain Res Dev Brain Res, vol. 140, no. 1, Jan. 2003, pp. 117–25. Pubmed, doi:10.1016/s0165-3806(02)00607-7.
Journal cover image

Published In

Brain Res Dev Brain Res

DOI

ISSN

0165-3806

Publication Date

January 10, 2003

Volume

140

Issue

1

Start / End Page

117 / 125

Location

Netherlands

Related Subject Headings

  • Signal Transduction
  • Reflex, Startle
  • Reflex
  • Protein Kinase C
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Posture
  • Neurology & Neurosurgery
  • Models, Animal
  • Mice