DECREASED BINDING OF DOPAMINE D3 RECEPTORS IN LIMBIC SUBREGIONS AFTERNEONATAL BILATERAL LESION OF RAT HIPPOCAMPUS

Neonatal, bilateral lesion of the ventral hippocampus (VH) in rats rec ently has been proposed as a model of schizophrenia because these anim als show postpubertal hypersensitivity to stress and to dopamine (DA) agonists that can be reversed by neuroleptic treatment. In search of t he mechanisms of postpubertal emergence of hyperdopaminergic behavior in this model, we investigated developmental expressions of DA D1, D2, and D3 receptors in various striatal and limbic subregions of rats th at had received bilateral ibotenic acid lesion of the VH at postnatal day 7 (PD7). D-Amphetamine-, apomorphine-, and stress-induced changes in locomotor activity were measured and, in accordance with previous r eports, we observed an increased locomotor activity at PD56 in the hip pocampal-lesioned group. The expression of DA D1, D2, and D3 receptors was then estimated in these rats by ligand autoradiography at PD41 an d PD62. We observed that the levels of DA D3 receptors, as measured by tritiated 7-hydroxy-N,N-di-n-propyl-2-amino-tetralin ([H-3]7-OH-DPAT) binding, are markedly reduced at PD62 in the limbic areas of lesioned rats compared with sham controls, particularly in the nucleus accumbe ns, olfactory tubercles, and islands of Calleja. A small but significa nt increase in D1 receptors was also seen in the caudate-putamen of th e lesioned animals at PD62, whereas no significant change in the overa ll expression of D2 receptors ([H-3]spiperone binding) was noted. In v iew of the inhibitory role of D3 receptors on locomotion and, presumab ly, other DA-mediated behaviors, it is suggested that behavioral chang es in the neonatally hippocampal-lesioned rats may be mediated by alte red D3 receptor levels.