The effect of dopamine D₁ receptor stimulation on the up-regulation of histamine H₃-receptors following destruction of the ascending dopaminergic neurones

1. The binding of [³H]-(R)α-methylhistamine and [³H]-N(α)-methylhistamine to histamine H₃-receptors, [³H]-SCH23390 to dopamine D₁-receptors, and [³H]-YM09151-2 to dopamine D₂-receptors was investigated by quantitative receptor autoradiography in the rat brain following 6-hydroxydopamine injection into the substantia nigra. 2. The levels of [³H]-(R)α-methylhistamine binding sites in the denervated striatum and substantia nigra were significantly higher than those in the contralateral side from 1 week to 12 weeks after nigral lesions. The H₃-receptor binding was maximal at 3 weeks after nigral lesions and maintained until 12 weeks. 3. The increased number of histamine H₃-receptors was decreased to the level of the contralateral side by chronic treatment with a selective dopamine D₁ agonist, SKF38393, but not modified by a selective dopamine D₂ agonist, quinpirole. 4. Dopamine D₁- and D₂-receptors in the striatum were similarly up-regulated after unilateral nigral lesion. On the other hand, the number of dopamine D₁-receptors in the substantia nigra was markedly decreased after administration of 6-hydroxydopamine. 5. The treatment with (S)α-fluoromethylhistidine increased the H₃-receptor binding in both the ipsilateral and contralateral sides. As a result, the magnitude of the ratio of the H₃-receptor binding between ipsilateral and contralateral sides was partially attenuated by treatment with (S)-α-fluoromethylhistidine. 6. These results strongly suggest that the expression of histamine H₃-receptors in the striatum and substantia nigra is influenced through D₁-receptors by tonic nigrostriatal dopaminergic inputs.