Enhancement of postsynaptic sensitivity to dopaminergic agonists induced by neonatal hippocampal lesions

The effects of neonatal hippocampal lesions on behavioral responsiveness to dopaminergic agonists and antagonists were examined. The ventral hippocampus was damaged bilaterally using ibotenic acid on postnatal day 7, and locomotor responses to dopaminergic agonists and antagonists were evaluated on postnatal day 35 (PD35), 56 (PD56), and 70 (PD70). Qunipirole (0.06, 0.125, 0.25, and 0.5 mg/kg SC), but not SKF38393 (5 and 10 mg/kg SC), increased locomotion in a dose-dependent manner in control and lesioned groups on PD35 and PD56. However, lesioned rats displayed a greater behavioral response to quinpirole than controls at the doses of 0.25 and 0.5 mg/kg on both PD35 and PD56. Amphetamine (1.5 mg/kg IP) increased locomotor activity in both groups on PD70, but this effect was greater in lesioned rats than in controls. Raclopride (0.25 and 0.5 mg/kg SC) and SCH23390 (0.01 and 0.02 mg/kg SC) blocked the amphetamine-induced hyperlocomotion in the lesioned and control groups. These results suggest that neonatal hippocampal lesion-induced behavioral hyperresponsiveness to amphetamine is likely related to an increased postsynaptic sensitivity of the D2 subtype of receptors.