Glutamate‐evoked release of endogenous brain dopamine: inhibition by an excitatory amino acid antagonist and an enkephalin analogue

Abstract

1 The present study examined the effect of a selective δ-opioid receptor agonist [d-Ala²-d-Leu⁵] enkephalin (DADL) on the spontaneous and the l-glutamic acid (l-Glu)-evoked release of endogenous dopamine from superfused slices of rat caudate-putamen. The amount of dopamine in slice superfusates was measured by a sensitive method employing high-performance liquid chromatography with electrochemical detection (h.p.l.c.-e.d.) after a two-step separation procedure. 2 The spontaneous release of endogenous dopamine was (a) partially dependent on Ca²⁺, (b) enhanced in Mg²⁺-free superfusion medium, (c) partially reduced by tetrodotoxin (TTX, 0.3 μm), (d) partially reduced by the putative excitatory amino acid receptor antagonist dl-2-amino-7-phosphonoheptanoic acid (dl-APH, 1 mm), and (f) increased 10 fold by the dopamine uptake blocker, nomifensine (10 μm). DADL (5 and 50 nm) did not significantly affect spontaneous dopamine release. 3 l-Glu (0.1–10 mm) produced a concentration-dependent release of endogenous dopamine from slices of caudate-putamen. This effect was (a) Ca²⁺-dependent, (b) strongly inhibited by 1.2 mm Mg²⁺, (c) attenuated by dl-APH (1 mm), (d) attenuated by TTX (0.3 μm), and (c) enhanced by nomifensine (10 μm). In the presence of nomifensine DADL (50 nm) reduced significantly the l-Glu-evoked release of endogenous dopamine by 20%. The inhibitory effect of DADL was blocked by 10 μm naloxone. 4 These results indicate tht l-Glu stimulates the Ca²⁺-dependent release of endogenous dopamine in the caudate-putamen by activation of N-methy-d-aspartate-type of excitatory amino acid receptors. This release can be selectively modified by the δ-opioid agonist DADL in a naloxone-sensitive manner.