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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Shahak, H; Slotkin, TA; Yanai, J

Published Date

  • January 2003

Published In

Volume / Issue

  • 140 / 1

Start / End Page

  • 117 - 125

PubMed ID

  • 12524182

Pubmed Central ID

  • 12524182

International Standard Serial Number (ISSN)

  • 0165-3806

Digital Object Identifier (DOI)

  • 10.1016/s0165-3806(02)00607-7

Language

  • eng