PMID- 12524182
OWN - NLM
STAT- MEDLINE
DCOM- 20030327
LR  - 20190901
IS  - 0165-3806 (Print)
IS  - 0165-3806 (Linking)
VI  - 140
IP  - 1
DP  - 2003 Jan 10
TI  - Alterations in PKCgamma in the mouse hippocampus after prenatal exposure to 
      heroin: a link from cell signaling to behavioral outcome.
PG  - 117-25
AB  - 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.
FAU - Shahak, Halit
AU  - Shahak H
AD  - 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.
FAU - Slotkin, Theodore A
AU  - Slotkin TA
FAU - Yanai, Joseph
AU  - Yanai J
LA  - eng
GR  - HD 40820/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res Dev Brain Res
JT  - Brain research. Developmental brain research
JID - 8908639
RN  - 70D95007SX (Heroin)
RN  - 8Y164V895Y (Carbachol)
RN  - EC 2.7.1.- (protein kinase C gamma)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects/*physiology
MH  - Body Weight/drug effects
MH  - Carbachol/pharmacology
MH  - Cell Membrane/enzymology
MH  - Enzyme Activation
MH  - Feeding Behavior/drug effects
MH  - Female
MH  - Heroin/*pharmacology
MH  - Hippocampus/drug effects/*enzymology
MH  - Maternal Behavior
MH  - Mice
MH  - Models, Animal
MH  - Posture
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Protein Kinase C/*metabolism
MH  - Reflex/drug effects/physiology
MH  - Reflex, Startle/drug effects
MH  - Signal Transduction/drug effects/physiology
EDAT- 2003/01/14 04:00
MHDA- 2003/03/28 05:00
CRDT- 2003/01/14 04:00
PHST- 2003/01/14 04:00 [pubmed]
PHST- 2003/03/28 05:00 [medline]
PHST- 2003/01/14 04:00 [entrez]
AID - S0165380602006077 [pii]
AID - 10.1016/s0165-3806(02)00607-7 [doi]
PST - ppublish
SO  - Brain Res Dev Brain Res. 2003 Jan 10;140(1):117-25. doi: 
      10.1016/s0165-3806(02)00607-7.