Subtypes of excitatory amino acid receptors involved in the stimulation of [ 3 H]dopamine release from cell cultures of rat ventral mesencephalon

N‐methyl‐D‐aspartic acid (NMDA), quisqualic acid (QUIS), and kainic acid (KAIN), respective agonists for three excitatory amino acid (EAA) receptor subtyes, stimulated [ 3 H]dopamine ([ 3 H]DA) release from dissociated cell cultures of fetal rat ventral mesencephalon. Release evoked by all three agonist was Ca 2+ ‐dependent and inhibited by broad‐spectrum antagonists (D, L‐ cis ‐2, 3‐piperidine dicarboxylic acid [PDA] and kynurenic acid [KYN]). However, both of these antagonists were more potent against KAIN than against QUIS and only KAIN‐evoked release was blocked by γ‐D‐glutamylaminomethyl sulfonic acid (GAMS, IC 50 700 m̈M). NMDA‐stimulated [ 3 H]DA release was selectively inhibited by competitive (3‐[2‐carboxypiperazine‐4‐yl]propyl‐1‐phosphonic acid [CPP] and D, L‐2‐amino‐5‐phosphonvaleric acid [APV]) and non‐competitive (phencyclidine and MK‐801) NMDA receptor antagonists. In 1.2 mM Mg 2+ , NMDA‐stimulated [ 3 H]DA release was NA + ‐dependent and inhibited by tetrodotoxin (TTX, 2 m̈M) or by the local anaesthetic, lidocaine (200 m̈M). However, in 0 Mg 2+ , NDMA‐evoked release was not inhibited by TTX or lidocaine. Thus, TTX‐sensitivity of the NMDA response in 1.2 mM Mg 2+ apparently occurs because Na + ‐action potentials are required to alleviate a Mg 2+ blockade. Neither QUIS‐nor KAIN‐evoked release was affected by Mg 2+ or TTX. When extracellular NaCI was replaced by sucrose or Na 2 SO 4 , the QUIS response was increased. KAIN‐evoked release was unaffected by the sucrose substitution and was attenuated in the Na 2 SO 4 ‐containing buffer. It is concluded that NMDA and QUIS/KAIN release [ 3 H]DA via separate receptor subtypes.