title: Alterations in PKCgamma in the mouse hippocampus after prenatal exposure to heroin: a link from cell signaling to behavioral outcome.
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 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.
authors.affiliation: The Ross Laboratory for Studies in Neural Birth Defects, Department of Anatomy and Cell Biology, The Hebrew University-Hadassah Medical School, P.O. Box 12272, 91120 Jerusalem, Israel.
authors.forename: Halit
authors.initials: H
authors.lastname: Shahak
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Slotkin
authors.forename: Joseph
authors.initials: J
authors.lastname: Yanai
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D003932:Heroin / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D008425:Maternal Behavior; D051379:Mice; D023421:Models, Animal; D011187:Posture; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011493:Protein Kinase C / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D003932:Heroin; D002217:Carbachol; C087857:protein kinase C gamma; D011493:Protein Kinase C