6-Hydroxydopamine lesion of locus coeruleus and the antiparkinsonian potential of NMDA-receptor antagonists in rats.

Behavioral and neurochemical effects after bilateral 6-hydroxy-dopamine locus coeruleus- (LC) lesion were examined in rats and compared to sham-lesioned controls. Behavior after treatment with the antiakinetic drugs dizocilpine, amantadine, memantine or L-DOPA as well as joint treatment of these drugs with haloperidol were tested in an open field with holeboard and in an experimental chamber. Under saline spontaneous activity (open field with holeboard) and sniffing (experimental chamber) were reduced after lesion. Injection of the proparkinsonian drug haloperidol decreased sniffing in all rats but to a greater extent in LC-lesioned rats. In combination with haloperidol none of the tested drugs 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 parkinsonian symptoms induced by blockade of dopamine D2-receptors, and lowers the antiakinetic potential of dizocilpine, amantadine, memantine or L-DOPA.