DIFFERENTIAL DOPAMINERGIC REGULATION OF THE NEUROTENSIN STRIATONIGRALAND STRIATOPALLIDAL PATHWAYS IN THE RAT

Recently the existence of a neurotensin striatonigral pathway strongly up-regulated by methamphetamine has been demonstrated. The aim of the present study was to investigate, using immunohistochemistry and radi oimmunoassay, the modulation of this pathway by dopamine antagonists. Rats were injected either with methamphetamine alone or together with the dopamine D-1 receptor antagonist, SCH 23390 (R(+)-7-chloro-8-hydro xy-3-methyl-1-phenyl-2 H-3-benzapine hydrochloride), or with the dopam ine D-2 receptor antagonist, sulpiride. Both techniques showed that th is neurotensin striatonigral pathway is regulated by dopamine D-1 rece ptors, since SCH 23390 totally prevented the methamphetamine-induced i ncrease in neurotensin-like immunoreactivity, both in the striatum and in the substantia nigra pars reticulata. Conversely, sulpiride was un able to counteract the effect of methamphetamine in these two areas, s uggesting that dopamine D-2 receptors are not involved in the regulati on of this neurotensin pathway. On the other hand, neurotensin-like im munoreactivity was markedly increased in striatal cell bodies and in t he globus pallidus after treatment with sulpiride, indicating that thi s pathway is mainly regulated by dopamine D-2 receptors.