Restorative plasticity of dopamine neuronal transplants depends on the degree of hemispheric dominance

The ability of dopaminergic (DA) transplants to restore complex sensorimoto r behaviors in experimental Parkinson's disease is dependent on graft survi val and reinnervation and is likely to be further modified by complex funct ional graft-host interactions. Here, we examined the impact of hemispheric dominance and extensive testing regimes on the functional capabilities of D A transplants to restore skilled forelimb movements in rats with unilateral 6-hydroxydopamine lesions. Interestingly, a near complete recovery was obs erved in DA-grafted animals that did not exhibit a strong hemispheric later alization for paw use before lesion and implantation surgery, whereas anima ls with a clear lateralization of paw use and grafted into the contralatera l hemisphere exhibited only moderate recovery. Finally, animals grafted ips ilateral to the preferred paw were most resistant to functional improvement s in skilled forelimb use. However, the influence of hemispheric dominance on the degree of functional DA graft-induced restoration was specific for s killed forelimb use, whereas no such differences were observed in other tes ts for motor and sensory functions related to the DA system. Furthermore, f unctional recovery of DA-grafted animals in skilled forelimb use was signif icantly promoted by extensive behavioral testing regimes indicative of a "l earning how to use" the transplant effect. These findings indicate the importance of the underlying functional archite cture of complex sensorimotor behaviors, such as skilled forelimb use, and the DA neurotransmitter system for the plasticity of DA transplants to prom oting a more complete behavioral recovery in experimental, and potentially, also in clinical forms of Parkinson's disease.