ENHANCEMENT OF POSTSYNAPTIC SENSITIVITY TO DOPAMINERGIC AGONISTS INDUCED BY NEONATAL HIPPOCAMPAL-LESIONS

The effects of neonatal hippocampal lesions on behavioral responsivene ss 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 antagonist s were evaluated on postnatal day 35 (PD35), 56 (PD56), and 70 (PD70). Quinpirole (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 d isplayed a greater behavioral response to quinpirole than control at t he 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 th is 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 th e amphetamine-induced hyperlocomotion in the lesioned and control grou ps. These results suggest that neonatal hippocampal lesion-induced beh avioral hyperresponsiveness to amphetamine is likely related to an inc reased postsynaptic sensitivity of the D-2 subtype of receptors. (C) 1 997 American College of Neuropsychopharmacology.