LOCALIZATION OF DOPAMINE-RECEPTOR SUBTYPES IN CORPUS STRIATUM AND NUCLEUS-ACCUMBENS-SEPTI OF RAT-BRAIN - COMPARISON OF D-1-LIKE, D-2-LIKE, AND D-4-LIKE RECEPTORS

Changes in D-1-, D-2- and D-4-like dopamine receptor binding in rat br ain were examined by quantitative autoradiography following: (i) unila teral surgical ablation of frontal cerebral cortex to remove descendin g projections to corpus striatum and nucleus accumbens, (ii) unilatera l 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 dopami ne projections. Rats were killed one week after lesioning, with contra lateral tissue controls. Radioligands were: [H-3]SCH-23390 for D-1-lik e (D-1/D-5) receptors, [H-3]nemonapride alone for D-2-like (D-2/D-3/D- 4) receptors, and [H-3]nemonapride with 300 nM S[-]-raclopride and oth er masking agents for D-4-like receptors (identified by blockade with D-4 selective L-745,870). Frontal cerebral cortex ablation did not alt er D-1- or D-2-like receptor density, but D-4-like binding decreased s ignificantly in both corpus striatum (18%) and nucleus accumbens (23%) . Kainic acid markedly reduced D-1-like (75% and 84%) and D-2-like bin ding (44% and 52%), with smaller D-4-like losses (28% and 27%) in corp us striatum and nucleus accumbens, respectively. Nigral 6-hydroxydopam ine lesions (verified by autoradiographic loss of dopamine transporter s labelled with [H-3]GBR-12935) did not significantly change D-1-, D-2 -, or D-4-like binding in the corpus striatum. These results suggest t hat the majority of D-1-, and D-2-like, and a smaller portion of D-4-l ike receptors in corpus striatum and nucleus accumbens arise on intrin sic postsynaptic neurons, and that some D-4-like, but neither D-1-nor D-2-like, receptors are found on presynaptic corticostriatal afferents . (C) 1997 IBRO. Published by Elsevier Science Ltd.