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

Abstract

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. 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. 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. 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. 1987 British Pharmacological Society