Pre- and postsynaptic alterations in the septohippocampal cholinergic innervations after prenatal exposure to drugs.
The present study was designed to evaluate possible presynaptic and postsynaptic alterations in the hippocampal cholinergic innervations that account for the hippocampus-related behavioral deficits found after prenatal drug exposure. Mice were prenatally exposed to either phenobarbital or heroin. On postnatal day 50, the hippocampi were removed and protein kinase C (PkC) activity, the amounts of Gi, Go, and Gq guanosine 5'-triphosphate binding proteins (G-proteins), and choline transports were determined. Basal PkC activity was higher than control levels in both phenobarbital and heroin treated mice, by 41% and 35%, respectively. The increase of PkC activity in response to carbachol was impaired in both treatment groups: in control mice, membrane PkC activity in hippocampal slices increased by 40%-50%, while no such response, or even slight reduction in PkC activity, was observed in the drug-exposed offspring. A significant increase was found in Gi and Gq G-proteins (18%-21%) in mice exposed to phenobarbital or to heroin compared with control levels. The amount of choline transporters, determined by hemicholinium binding, increased by 70% compared with the control level in mice prenatally exposed to heroin, and increased by 71% in mice prenatally exposed to phenobarbital. The alterations in basal and carbachol-stimulated hippocampal PkC activity after prenatal drug exposure may be related to an impairment in long-term potentiation (LTP); which plays an important role in hippocampal related behavioral abilities, changes in which are caused by prenatal drug exposure.
Department of Anatomy and Embryology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
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RA
Steingart
J
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Barg
J
J
Maslaton
M
M
Nesher
J
J
Yanai
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D003932:Heroin / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017729:Presynaptic Terminals / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012688:Septum Pellucidum / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000502:physiology
D003932:Heroin; D002217:Carbachol; D011493:Protein Kinase C; D010634:Phenobarbital