Biopsychological study on the compensation mechanism of brain dopaminergic system in animal model of hyperactivity

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Treatment of neonatal rats with intracerebral 6-hydroxydopamine produces a marked depletion of brain dopamine (DA) and locomotor hyperactivity during preweaning period. In order to investigate the brain reward system in this animal model of hyperactivity, we tested conditioned place preference (CPP) by methamphetamine (MAP) using a CPP test apparatus. Neonatally DA-lesioned rats showed conditioned preference to MAP compartment to the same extent as control rats, suggesting normal functioning of brain reward system. Biochemical analysis of brain DA levels in the accumbens nucleus which is the terminal area of brain DA system showed that DA concentration in this area was below 30% of control animals, however according to a microdialysis study the extracellular levels of DA was almost equal to that of control animals. This suggests DA system damaged at neonatal period shows compensation in the accumbens nucleus.It has been known that midbrain DA neurons have neurotensin (NT) receptors on their cell bodies. We investigated the effect of intracerebral NT injection on the extracellular levels of DA in the accumbens nucleus. The increase of DA levels induced by NT injection was more remarkable in neonatally DA-lesioned rats. This suggests that NT is involved in compensation mechanism of brain dopaminergic system in animal model of hyperactivity.