Cholecystokinin-dependent regulation of host dopamine inputs to striatal grafts

Intrastriatal infusions of cholecystokinin-8-sulphate in the rat exerts a dose-dependent inhibition of dopamine-release from nigrostriatal terminals in the neostriatum, as measured by push-pull perfusion. This effect is abolished by excitotoxic lesions of the neostriatum, which, along with behavioural, electrophysiological and receptor binding studies, suggests that cholecystokinin exerts its action indirectly on dopamine release via receptors located on intrinsic striatal neurons. Grafts of embryonic striatum implanted in the lesioned striatum become innervated by host-derived dopamine axons and restore the response of those host neurons to cholecystokinin infusion. This suggests that the innervation of the grafts by dopaminergic axons of the host brain does not simply provide a tonic input to the grafts, but rather represents a phasic input that is under dynamic local regulation by graft-host feedback influences from the transplanted neurons themselves.