ALTERATIONS IN HIPPOCAMPAL HEMICHOLINIUM-3 BINDING AND RELATED BEHAVIORAL AND BIOCHEMICAL-CHANGES AFTER PRENATAL PHENOBARBITONE EXPOSURE

Previous studies demonstrated postsynaptic septohippocampal cholinergi c alterations after early exposure to phenobarbital: The present study was designed to ascertain possible corresponding presynaptic alterati ons while confirming the known behavioral deficits and extending previ ous findings on postsynaptic; cholinergic alterations. Pregnant hetero geneous mice received-milled mouse food containing 3 g/kg phenobarbita l on gestation days 9-18. At age 50 days, [H-3]hemicholinium-3 binding , which labels the presynaptic transporter for high affinity choline u ptake, was increased in treated mice by 100% (P < 0.001). This change was not accompanied by a change in the affinity of the transporter to the ligand. Another group of offspring was tested for hippocampus-rela ted behaviors. Consistent with our previous studies in-the Morris maze , treated animals took longer to reach the platform in the place test as compared control, and swam fewer times over the missing platform lo cation in the spatial probe test. In the eight-arm maze, the treated o ffspring needed more entries than control to visit all the arms. In th e spontaneous alternation test, the treated mice showed fewer alternat ions than controls. Biochemically, as in our previous results prenatal phenobarbital exposure resulted in an increase in the degree of stimu lation of inositol phosphate formation by carbachol (P < 0.05), an act ion presumed to occur at postsynaptic muscarinic receptors. While the present results show that the effect of a combination of raised Kt in the presence of physostigmine and carbachol was significantly greater in barbiturate-treated mice (P < 0.05), the action of K+ in the presen ce of physostigmine, but without carbachol, was not-affected by the ph enobarbital treatment. The results point to the uniqueness of outcome of early insults where alterations along nerve conduction cascades do not necessarily follow the common rules in that upregulation could sim ultaneously occur both pre-and post synaptically.