Alterations in mice dopamine receptor characteristics after early exposure to phenobarbital

The present experiment was designed to study the sensitivity of dopamine (DA) receptors after early (pre- and neonatal) administration of phenobarbital (PhB). These receptors have been implicated in some of the behaviors which are altered by early barbiturate exposure. Pregnant HS mice were exposed to PhB (3 g/kg milled food) from the 9th to the 18th day of gestation. Their offspring were the subjects of the prenatal studies. The neonatal treatment consisted of daily injections of PhB to pups from ages 2 to 21 days (50 mg/kg PhB). Striata of treated animals and controls from both treatments, prenatal (PreB) and neonatal (NeoB) were removed at 22 or 50 days for DA receptor binding assay. Using Scatchard plot analysis of [³H]spiroperidol specific binding, long-term increase from control level in DA receptor number (B_max) was found in the PreB mice, while NeoB mice had decreased B_max (P < 0.001). No differences were found in the respective K_D values. In parallel psychopharmacological studies, PreB mice had increased apomorphine-induced climbing behavior response, and in previous studies we showed that NeoB had decreased apomorphine induced-climbing behavior response. The long-term alterations in DA receptor number may possibly mediate the changes in brain sensitivity to barbiturate and alcohol found in our previous studies.