NEONATAL HIPPOCAMPAL-LESIONS INDUCED HYPERRESPONSIVENESS TO AMPHETAMINE - BEHAVIORAL AND IN-VIVO MICRODIALYSIS STUDIES

The effect of neonatal hippocampal lesions on behavioral sensitivity t o amphetamine (AMPH) and dopamine (DA) release in the nucleus accumben s (NAc) were examined. The ventral hippocampus was damaged bilaterally by ibotenic acid on postnatal day 7 (PD7). Spontaneous exploration an d AMPH-stimulated locomotor activity were examined on postnatal day 35 (PD35) and day 56 (PD56). Extracellular DA, dihydroxyphenylacetic aci d (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5- HIAA) were sampled using in vivo microdialysis while simultaneously AM PH-stimulated locomotion was examined in freely moving rats on PD56. S pontaneous exploration increased in rats with hippocampal lesions rela tive to controls on PD56 but not PD35. AMPH (0, 0.187, 0.375, 0.75, 1. 5, and 3 mg/kg) enhanced locomotion dose-dependently in both control a nd lesioned groups. Locomotor activity was higher in lesioned rats tha n controls following AMPH at the dose of 0.75 mg/kg on PD35 and at the doses of 1.5 and 3.0 mg/kg on PD56. The basal level of DA in the NAc was not different between the hippocampal and control groups. AMPH (1. 5 mg/kg) induced hyperlocomotion in lesioned rats relative to controls . DA release in the NAc for both groups was enhanced following injecti ons of AMPH. However, neonatal hippocampal lesions had no further enha ncement on AMPH-stimulated release of DA as compared to the control gr oup. The levels of DOPAC and HVA in the NAc were altered by AMPH but n ot lesions. The level of 5-HIAA was not influenced by either lesions o r AMPH. The results of neonatal lesion-induced hyperlocomotion suggest that an emergence of behavioral hyperresponsiveness to AMPH was depen dent on an interaction of lesions, age of examination, and dose of the drug. A dissociation between the effect of AMPH on lesion-enhanced hy perlocomotion and a lack of a lesion-enhanced DA release in the NAc su ggest that presynaptic release of DA had no major contribution to lesi on-enhanced DA transmission in the mesolimbic DA system.