TY - JOUR
T1 - Alterations in PKCγ in the mouse hippocampus after prenatal exposure to heroin
T2 - A link from cell signaling to behavioral outcome
AU - Shahak, Halit
AU - Slotkin, Theodore A.
AU - Yanai, Joseph
PY - 2003/1/13
Y1 - 2003/1/13
N2 - 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.
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 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.
KW - Carbachol
KW - Heroin
KW - Hippocampus
KW - Mouse
KW - PKCα
KW - PKCγ
KW - Prenatal exposure
UR - http://www.scopus.com/inward/record.url?scp=0037428404&partnerID=8YFLogxK
U2 - 10.1016/S0165-3806(02)00607-7
DO - 10.1016/S0165-3806(02)00607-7
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C2 - 12524182
AN - SCOPUS:0037428404
SN - 0165-3806
VL - 140
SP - 117
EP - 125
JO - Developmental Brain Research
JF - Developmental Brain Research
IS - 1
ER -