6-HYDROXYDOPAMINE LESION OF LOCUS-COERULEUS AND THE ANTIPARKINSONIAN POTENTIAL OF NMDA-RECEPTOR ANTAGONISTS IN RATS

Behavioral and neurochemical effects after bilateral 6-hydroxy-dopamin e locus coeruleus- (LC) lesion were examined in rats and compared to s ham-lesioned controls. Behavior after treatment with the antiakinetic drugs dizocilpine, amantadine, memantine or L-DOPA as well as joint tr eatment of these drugs with haloperidol were tested in an open field w ith holeboard and in an experimental chamber. Under saline spontaneous activity (open field with holeboard) and sniffing (experimental chamb er) were reduced after lesion. Injection of the proparkinsonian drug h aloperidol decreased sniffing in all rats but to a greater extent in L C-lesioned rats. In combination with haloperidol none of the tested dr ugs could completely compensate for the motor deficits induced by the lesion. Neurochemical data revealed a reduced content of noradrenaline in the prefrontal cortex and in the posterior striatum of LC-lesioned rats. These results indicate that loss of LC neurons intensifies park insonian symptoms induced by blockade of dopamine D2-receptors, and lo wers the antiakinetic potential of dizocilpine, amantadine, memantine or L-DOPA.