Localization of dopamine receptor subtypes in corpus striatum and nucleus accumbens septi of rat brain: comparison of D1-, D2-, and D4-like receptors.

摘要

Changes in D1-, D2- and D4-like dopamine receptor binding in rat brain were examined by quantitative autoradiography following: (i) unilateral surgical ablation of frontal cerebral cortex to remove descending projections to corpus striatum and nucleus accumbens, (ii) unilateral injections of kainic acid into corpus striatum or nucleus accumbens to degenerate local intrinsic neurons, (iii) unilateral injections of 6-hydroxydopamine into substantia nigra to degenerate ascending dopamine projections. Rats were killed one week after lesioning, with contralateral tissue controls. Radioligands were: [3H]SCH-23390 for D1-like (D1/D5) receptors, [3H]nemonapride alone for D2-like (D2/D3/D4) receptors, and [3H]nemonapride with 300 nM S[-]-raclopride and other masking agents for D4-like receptors (identified by blockade with D4 selective L-745,870). Frontal cerebral cortex ablation did not alter D1- or D2-like receptor density, but D4-like binding decreased significantly in both corpus striatum (18%) and nucleus accumbens (23%). Kainic acid markedly reduced D1-like (75% and 84%) and D2-like binding (44% and 52%), with smaller D4-like losses (28% and 27%) in corpus striatum and nucleus accumbens, respectively. Nigral 6-hydroxydopamine lesions (verified by autoradiographic loss of dopamine transporters labelled with [3H]GBR-12935) did not significantly change D1-, D2-, or D4-like binding in the corpus striatum. These results suggest that the majority of D1-, and D2-like, and a smaller portion of D4-like receptors in corpus striatum and nucleus accumbens arise on intrinsic postsynaptic neurons, and that some D4-like, but neither D1- nor D2-like, receptors are found on presynaptic corticostriatal afferents.