MODULATION OF DOPAMINE D-1-MEDIATED TURNING BEHAVIOR AND STRIATAL C-FOS EXPRESSION BY THE SUBSTANTIA-NIGRA

In order to study the possible contribution of the substantia nigra (S N) in the positive interaction between dopamine D-1 receptor agonists and glutamate antagonists in unilaterally 6-hydroxydopamine (6-OHDA) l esioned rats, the effect of the D-1 agonist, SKF 38393, was studied in combination with intranigral infusions of glutamate antagonists of th e NMDA (MK 801, CPP) or AMPA (NBQX) type of receptor. Local infusion i nto the SN of the 6-OHDA lesioned side of MK 801, CPP or NBQX at doses inducing no or minimal behavioral effects significantly increased the turning behavior and the expression of c-fos induced, in the lesioned caudate-putamen (CPu), by a parenteral administration of SKF 38393. T he same result was obtained after intra-SN infusion of the GABA agonis t, muscimol. High doses of MK 801, CPP or muscimol infused into the SN produced intense contralateral turning per se and induced a sparse c- fos expression in the lesioned CPu which was antagonized by parenteral administration of MK 801. The results indicate that a depression of S N pars reticulata efferent neurons potentiates D-1-mediated responses and suggest that this area may play a role in the positive interaction between glutamate antagonists and D-1 receptor agonists. (C) 1995 Wil ey-Liss, Inc.