Abstract
Pregnant female mice were exposed to heroin on gestation days 9–18. On postnatal day 50, offspring showed marked deficits in the hippocampus related behaviors, eight-arm and Morris mazes. Alterations in the septohippocampal cholinergic innervations were studied as the possible mechanisms. We have found, presynaptically, that the binding of [ 3H]hemicholinium-3 (HC-3) (a reliable indicator of presynaptic cholinergic innervation) increased in the heroin exposed animals. The B max values of binding to muscarinic receptors (an indicator of postsynaptic cholinergic activity) increased as well. In agreement with this observation, carbachol induced formation of inositol phosphates (IP) similarly increased. Interestingly, we have also observed an increase in the levels of a subunit of several GTP binding proteins (Gai and Gaq). In addition, the basal level of Protein Kinase C (PKC) increased. However, PKC activity was unresponsive to acetylcholine agonist stimulation in the heroin treated animals, pointing to a possible explanation for the behavioral deficits.
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