INOSITOL PHOSPHATE FORMATION IN MICE PRENATALLY EXPOSED TO DRUGS - RELATION TO MUSCARINIC RECEPTORS AND POSTRECEPTOR EFFECTS

Mice were exposed to phenobarbital or heroin [diacetylmorphine (DAM)] prenatally by feeding the mother phenobarbital on gestation days 9-18; DAM was injected into the mother on gestation days 9-18. At the age o f 50 days, mice exposed to phenobarbital or DAM prenatally were examin ed for long-term biochemical changes in the postsynaptic septohippocam pal system as measured by alterations in formation of the second messe nger inositol phosphate (IP). A significant increase in IP formation i n response to carbachol was found after prenatal exposure to DAM, An i ncrease in IP formation in response to 20 mM KCl alone or in the addit ional presence of 10 mM carbachol or 1 mM physostigmine was found afte r prenatal exposure to phenobarbital or DAM. In addition, a significan t increase in IP formation in response to sodium fluoride was found af ter prenatal exposure to phenobarbital or DAM. It is suggested that an increase in G-protein activation and in the second messenger formatio n accompanies the early drug-induced upregulation of the muscarinic re ceptors found in our previous studies.