REVERSAL OF EARLY PHENOBARBITAL-INDUCED CHOLINERGIC AND RELATED BEHAVIORAL DEFICITS BY NEURONAL GRAFTING

The present experiment was performed to assess the possible restoratio n of normal maze behavior, as well as parallel muscarinic receptor bin ding capabilities, in mice pre- or neonatally exposed to phenobarbital . Mice were exposed to phenobarbital prenatally by feeding the mother phenobarbital (3 gkg milled food) on gestation days 9-18 (PreB mice), or neonatally, by daily injections of 50 mg/kg Na phenobarbital to the pups on days 2-21 (NeoB). At adulthood, PreB and NeoB mice were 61.3% and 65% deficient, respectively, in the hippocampus-related Morris ma ze behavior, as compared to control. Both groups had a 58% increase in their hippocampal muscarinic receptors maximal binding (B(max)) (p < 0.001); the dissociation constant (K(d)) was not affected by the pheno barbital exposure. Treated animals and their respective controls recei ved septal cholinergic embryonic graft into the hippocampus. The viabi lity of the transplants was confirmed by AChE histochemistry. Nine wee ks later the grafted mice showed significant improvement in the Morris maze (52% for both PreB and NeoB (p < 0.001)). Their B(max) was also reduced from early phenobarbital exposed animals' levels by 15% for Pr eB and by 25% for NeoB (p < 0.001). The results suggest that early phe nobarbital-induced behavioral deficit and their related biochemical al terations can be partially corrected by the appropriate neural graftin g, and thus provide further support to the apparent relationship betwe en the early phenobarbital-induced septohippocampal cholinergic altera tions and the hippocampus-related behavioral deficits.