Differential behavioral effects of partial bilateral lesions of ventral tegmental area or substantia nigra pars compacta in rats

Akinesia (or absence of movement) is a prominent feature of Parkinson's disease. Akinetic symptoms, however, are also observed in depression and schizophrenia, which support the hypothesis that akinesia involves more than only motor behavior. A common feature of these disorders is the disruption of dopamine homeostasis in the CNS. Here we aimed at relating the respective involvement of the nigrostriatal and mesocortical dopaminergic pathways to akinesia. We investigated in the rat the relative effects of selective bilateral partial lesions of substantia nigra pars compacta (SNc) or ventral tegmental area (VTA) which did not affect locomotion, on fine motor, motivational and cognitive behaviors. Motor impairments were measured by the evaluation of fine motor control in the stepping test and in the paw reaching test. Cognitive functions were assessed by various paradigms: spontaneous alternation in the Y maze and object exploration task. Motivational behavior was evaluated by the 100-pellets test. The results suggested that specific behavioral impairments are obtained following selective lesions of either SNc or VTA. SNc-lesioned rats exhibited deficits in fine motor functions as previously described in animal models of Parkinson's disease, whereas VTA-lesioned rats demonstrated traits of perseveration without significant motor impairments.