Studies on noradrenergic alterations in relation to early phenobarbital-induced behavioral changes

Mice were exposed to phenobarbital prenatally (B offspring) by feeding their mother 3 g/kg phenobarbital in milled food on gestation days 9-18; control dams received unadulterated milled food. At age 50 days, B offspring had fewer fluorescing noradrenergic (NE) cells in the locus coeruleus than control (P less than 0.001). Hippocampal NE levels were also lower in B than in control offspring, while the cerebellar NE levels of B offspring remained normal. Since B offspring are known to be deficient in their hippocampal eight-arm maze behavior, an attempt was made to reverse the behavioral deficit by transplantation of normal embryonic locus coeruleus NE cells into the impaired hippocampus of B offspring. While sham and NE-transplanted controls needed approximately 2 days to reach criterion in the maze, sham-transplanted B required approximately 5 days to reach criterion (P less than 0.01). The scores of NE-transplanted B mice were similar to B and differed significantly from control (P less than 0.01). Thus, it appears that the hippocampal behavioral deficits studied may not be related to alterations in locus coeruleus-hippocampal NE innervations.