PRE-SYNAPTIC AND POSTSYNAPTIC ALTERATIONS IN THE SEPTOHIPPOCAMPAL CHOLINERGIC INNERVATIONS AFTER PRENATAL EXPOSURE TO DRUGS

The present study was designed to evaluate possible presynaptic and po stsynaptic alterations in the hippocampal cholinergic innervations tha t account for the hippocampus-related behavioral deficits found after prenatal drug exposure, Mice were prenatally exposed to either phenoba rbital or heroin. On postnatal day 50, the hippocampi were removed and protein kinase C (PkC) activity, the amounts of Gi, Go, and Go guanos ine 5'-triphosphate binding proteins (G-proteins), and choline transpo rts were determined. Basal PkC activity was higher than control levels in both phenobarbital and heroin treated mice, by 41% and 35%, respec tively. The increase of PkC activity in response to carbachol was impa ired 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-expos ed offspring. A significant increase was found in Gi and Go G-proteins (18%-21%) in mice exposed to phenobarbital or to heroin compared with control levels. The amount of choline transporters, determined by hem icholinium binding, increased by 70% compared with the control level i n mice prenatally exposed to heroin, and increased by 71% in mice pren atally exposed to phenobarbital, The alterations in basal and carbacho l-stimulated hippocampal PkC activity after prenatal drug exposure may be related to an impairment in longterm potentiation (LTP); which pla ys an important role in hippocampal related behavioral abilities, chan ges in which are caused by prenatal drug exposure. (C) 1998 Elsevier S cience Inc.