DISTINCT PRESYNAPTIC CONTROL OF DOPAMINE RELEASE IN STRIOSOMAL-ENRICHED AND MATRIX-ENRICHED AREAS OF THE RAT STRIATUM BY SELECTIVE AGONISTS OF NK1, NK2, AND NK3 TACHYKININ RECEPTORS

Using a sensitive in vitro microperfusion method, the effects of selective and potent agonists of NK1, NK2, and NK3 tachykinin receptors {[Pro9]SP, [Lys5,MeLeu9, Nle10]NKA-(4-10), and [Pro7]NKB, respectively} on the presynaptic control of dopamine release were investigated in striosomal-enriched (area rich in [H-3]naloxone binding sites) and matrix-enriched areas of the rat striatum. Marked differences could be demonstrated as follows: (i) when used at 0.1 muM, the NK1 agonist stimulated the release of [H-3]dopamine continuously synthesized from [H-3]tyrosine in both compartments, while the NK2 and NK3 agonists enhanced the release of [H-3]dopamine only in the matrix; (ii) the stimulatory effect of the NK3 agonist was less pronounced than those of the NK1 and NK2 agonists; (iii) the NK1 agonist-evoked responses were tetrodotoxin (1 muM) sensitive, while those of the NK2 and NK3 agonists were, respectively, partially and totally tetrodotoxin resistant; (iv) specific receptors are involved in these responses since the stimulatory effects of the NK1 and NK2 agonists were, respectively, blocked by potent antagonists of NK1 (RP-67580; 1 muM) and NK2 (SR-48968; 1 muM) receptors, while these antagonists did not affect the NK3 agonist-evoked response; (v) the indirect stimulatory effect of the NK1 agonist was partially reduced under local blockade of cholinergic transmission in the matrix but not in the striosomal-enriched area. Interestingly, this study also revealed mismatches between autoradiographic data and receptor-mediated responses, since NK2 binding sites could not be observed in the striatum while NK3 but not NK1 binding sites were visualized in the striosomal-enriched area.