Changes in striatal dopaminergic behavior after early exposure to barbiturate

Exposure to barbiturate during development modifies behaviors in a manner often similar to the effect of mutations (e.g., induction of audiogenic seizure susceptibility). It has been noticed that many of these behaviors are related to the dopaminergic system. In order to assess the possible dopaminergic mediation of the apparent phenocopies produced by early barbiturate administration, heterogeneous HS/Ibg mice were injected daily with 50 mg/kg phenobarbital (PhB) from age 2 to 21 days (group B), while control littermates received vehicle injections. Control and group B mice were then tested for striatal climbing behavior induced by 2 or 5 mg/kg apomorphine, at ages 22, 28, 35, and 44 days. At age 22 days group B mice had reductions of climbing from control levels of 44 and 41% for 2 and 5 mg apomorphine, respectively (P < 0.01), regardless of sex differences. On day 28 the respective reductions were 16 and 32% (P < 0.05). The differences on the days 35 and 44 were small and did not reach statistical significance. Since climbing has been found to be induced primarily by postsynaptic striatal dopaminergic receptors, it is suggested that neonatal PhB exposure induces subsensitivity of the striatal postsynaptic dopamine receptors. The present findings support other studies implicating postsynaptic striatal dopamine receptors in the behavioral alterations induced by early PhB exposure. The results further support our previous finding of the lessened response to apomorphine-induced hypothermia after prenatal exposure to barbiturate.