Decreased binding of dopamine D3 receptors in limbic subregions after neonatal bilateral lesion of rat hippocampus

Neonatal, bilateral lesion of the ventral hippocampus (VH) in rats recently has been proposed as a model of schizophrenia because these animals show postpubertal hypersensitivity to stress and to dopamine (DA) agonists that can be reversed by neuroleptic treatment. In search of the 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 that 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 reports, we observed an increased locomotor activity at PD56 in the hippocampal-lesioned group. The expression of DA D1, D2, and D3 receptors was then estimated in these rats by ligand autoradiography at PD41 and PD62. We observed that the levels of DA D3 receptors, as measured by tritiated 7-hydroxy-N,N-di-n-propyl-2-amino-tetralin ([3H]7-OH-DPAT) binding, are markedly reduced at PD62 in the limbic areas of lesioned rats compared with sham controls particularly in the nucleus accumbens, olfactory tubercles, and islands of Calleja. A small but significant increase in D1 receptors was also seen in the caudate-putamen of the lesioned animals at PD62, whereas no significant change in the overall expression of D2 receptors ([3H]spiperone binding) was noted. In view of the inhibitory role of D3 receptors on locomotion and, presumably, other DA-mediated behaviors, it is suggested that behavioral changes in the neonatally hippocampal-lesioned rats may be mediated by altered D3 receptor levels.