Behavioural recovery following transplantation of substantia nigra in rats subjected to 6-OHDA lesions of the nigrostriatal pathway. I. Unilateral lesions

Abstract

The ability of embryonic substantia nigra transplants to compensate for behavioural deficits induced by unilateral destruction of the nigrostriatal dopamine pathway has been investigated in adult rats. Six days following unilateral 6-OHDA lesions of the nigrostriatal pathway, the adequacy of the lesion was assessed by measurement of the intensity of ipsilateral amphetamine-induced rotation. All rats then received surgical cavities in the cortex overlying the head of the caudate-putamen on the lesioned side. In 51 rats, transplants of embryonic substantia nigra were placed on the dorsal surface of the caudate-putamen, and the remaining 19 rats served as unilateral lesioned controls. Behavioural testing was conducted approximately 3 months after transplantation: (a) the transplant animals alone showed a marked reduction in ipsilateral rotation induced by 5 mg/kg amphetamine (‘compensation’); (b) although both transplanted and control rats expressed equal contralateral rotation at a dose of 0.25 mg/kg apomorphine, the transplant animals alone showed a marked reduction in rotation at a lower dose of 0.05 mg/kg; (c) the transplanted rats showed less asymmetry in spontaneous rotational behaviour than controls, and the asymmetry was further reduced by mild tailpinch; (d) when tested for spontaneous choice behaviour in a T-maze, control rats showed 97% selection of the arm ipsilateral to the 6-OHDA lesion, whereas the transplanted rats that were well compensated on the amphetamine rotation test turned to the contralateral side on 30–40% of choices; (e) no transplant-induced changes were found in contralateral sensory inattention on a sensorimotor test battery, whether tested spontaneously or under mild tailpinch-induced activation. The results support the conclusion that dopaminergic reinnervation of the dorsal neostriatum is capable of inducing functional recovery in many, but not all, behavioural tests which involve side choice or bias, not only after pharmacological activation but also in the spontaneous behaving animal.