(L)-DOPA produces strong induction of c-fos messenger RNA in dopamine-denervated cortical and striatal areas of the common marmoset

Common marmosets (Callithrix jacchus) with near-complete unilateral 6-hydro xydopamine denervation of the dopaminergic input received a single injectio n of saline or L-DOPA (15 mg/kg plus 6.25 mg/kg benserazide). Using in situ hybridization , the effects of these treatments on c-fos messenger RNA exp ression in the cerebral cortex, the striatal complex and the external layer of the pallidum were studied. Moreover, receptor autoradiography was used to determine the levels of dopamine D-1 and D-2 receptors in these areas. I n the cerebral cortex, animals treated with L-DOPA displayed a high express ion of c-fas messenger RNA restricted to the dopamine-denervated hemisphere . No changes in the levels of cortical D-1 and D-2 receptors were found in the dopamine-denervated hemisphere. L-DOPA treatment also induced a strong expression of c-Sos messenger RNA in the striatal complex in the dopamine-d enervated hemisphere. The levels of striatal D-2, but not D-1, receptors we re increased in the dopamine denervated hemisphere. In the external pallidu m, the major terminal region for DL dopamine receptor-containing striatal p rojection neurons, L-DOPA treatment induced c-Sos messenger RNA expression in both the intact and the dopamine-denervated hemispheres. Thus, using c-fos messenger RNA as a biochemical marker of postsynaptic neu ronal activation, these results provide evidence that near-complete dopamin e depletion causes a profound supersensitization to L-DOPA treatment in the cerebral cortex and in the striatal complex, but not in the external layer of the pallidum, of the primate brain. The cortical response may be unique to the primate brain, but c-fos messenger RNA activation within the striat um has also been reported in the rodent. The effects of L-DOPA probably dep end both on a direct activation of supersensitized dopamine receptors by do pamine produced in the few remaining, but hyperactive, dopaminergic nerve t erminals and in serotonergic nerve terminals, as well as on indirect action s of L-DOPA related to activation of circuitries connecting cerebral cortex and basal ganglia structures. These results provide novel information on t he mechanisms underlying L-DOPA's action in the cerebral cortex, striatum a nd external pallidum in a primate model of Parkinson's disease. (C) 2000 IB RO. Published by Elsevier Science Ltd. All rights reserved.