Long-term reduction in spontaneous alternations after early exposure to phenobarbital

Spontaneous alternation behavior is related to the integrity of the hippocampus. Our earlier studies demonstrated hippocampal deficits after early phenobarbital (PhB) exposure. In the present study, we examined spontaneous alternation of mice who had been exposed to PhB prenatally or neonatally. Prenatal PhB was administered transplacentally: pregnant females were fed 3 g PhB/kg milled food on gestation days 9-18. Neonates were treated directly with daily injections of 50 mg PhB/kg on postnatal days 2-22. The animals were tested for spontaneous alternation in a T maze at the ages of 22, 28, 35 and 42 days. The test was conducted at each age for two consecutive days. A maximum of four alternations were allowed on the first day, and one alternation on the second day. Animals treated neonatally had reductions in alternation from the control group for every age group. Looking at the mean of the four trials on the first day there was a reduction of 35% at age 22 (P < 0.001), 8% at age 28, 21% at age 35 (P < 0.05) and 36% at age 42 (P < 0.02). On the second day the respective reductions were 32, 19, 24 and 36% (P < 0.05). The differences in alternation between animals treated with PhB prenatally and the control group were too small to reach statistical significance. Subsequently a more sensitive test, delayed spontaneous alternation (30 s), was applied to an additional group of animals at age 42 which had been prenatally exposed to PhB: 31% reduction from the control group was found on day 1 (P < 0.001), and 34% on day 2 (P < 0.02). The greater differences after neonatal as opposed to prenatal administration could be related to the more extensive hippocampal damage that was found in adults after neonatal treatment.