Localization of dopamine receptor subtypes in corpus striatum and nucleus accumbens septi of rat brain: comparison of D 1-, D 2- and D 4-like receptors

Abstract

Changes in D 1-, D 2- and D 4-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 D 1-like ( D 1/D 5 ) receptors, [ 3H]nemonapride alone for D 2-like (D 2/D 3/D 4) receptors, and [ 3H]nemonapride with 300 nM S[−]-raclopride and other masking agents for D 4-like receptors (identified by blockade with D 4 selective L-745, 870). Frontal cerebral cortex ablation did not alter D 1- or D 2-like receptor density, but D 4-like binding decreased significantly in both corpus striatum (18%) and nucleus accumbens (23%). Kainic acid markedly reduced D 1-like (75% and 84%) and D 2-like binding (44% and 52%), with smaller D 4-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 D 1-, D 2-, or D 4-like binding in the corpus striatum. These results suggest that the majority of D 1-, and D 2 -like, and a smaller portion of D 4-like receptors in corpus striatum and nucleus accumbens arise on intrinsic postsynaptic neurons, and that some D 4-like, but neither D 1- nor D 2-like, receptors are found on presynaptic corticostriatal afferents.