Autoradiographic studies in animal models of hemi-parkinsonism reveal dopamine D 2 but not D 1 receptor supersensitivity. II. Unilateral intra-carotid infusion of MPTP in the monkey ( Macaca fascicularis)

Abstract

The selective dopaminergic antagonist ligands [ 3H]SCH 23390 and [ 3H]sulpiride were used to reveal autoradiographically dopamine D 1 and D 2 receptors, respectively, in brain sections from monkeys which had received unilateral intracarotid infusions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causing loss of dopamine-containing neurones of the substantia nigra pars compacta. The monkeys developed hemi-parkinsonian symptoms (tremor, bradykinesia) in limbs contralateral to the side of the toxin infusion. Administration of apomorphine (0.05–0.25 mg/kg) caused contralateral rotational behaviour, and reversal of the parkinsonian symptoms. Loss of forebrain dopaminergic terminals was assessed autoradiographically using [ 3H]mazindol to label dopamine uptake sites. A reduction in these sites of 97% (mean brain value) in the caudate nucleus, and 91% in the putamen, as compared with binding values from untreated control monkeys, was accompanied by a significant increase in the binding of [ 3H]sulpiride (D 2) in these structures. In contrast, in the same animals there was no similar increase in [ 3H]SCH 23390 binding to D 1 receptors in the denervated areas. These results suggest that in the parkinsonian brain, where the dopaminergic innervation of the caudate nucleus and putamen has been lost, D 2 receptors may be more susceptible than D 1 receptors to changes, revealed here as an increase in [ 3H]sulpiride binding sites.