Midbrain dopamine neurons in vivo discharge in a single-spike firing pattern or in a burst-firing pattern. Such activity in vivo strikingly contrasts with the pacemaker activity of the same dopamine neurons recorded in vitro. We have recently shown that burst activity in vivo of midbrain dopamine neurons is due to the local activation of excitatory amino acid receptors, as microapplication of the broad-spectrum antagonist of excitatory amino acids, kynurenic acid, strongly regularized the spontaneous firing pattern of these dopamine neurons. In the present study, we investigated which subtypes of excitatory amino acid receptors are involved in the burst-firing of midbrain dopamine neurons in chloral hydrate-anaesthetized rats, iontophoretic or pressure microejections of 6-cyano, 7-nitroquinoxaline-2,3-dione (CNQX), a non-N-methyl-D-aspartate (NMDA) receptor antagonist, did not alter the spontaneous burst firing of dopamine neurons (n = 36). In contrast, similar ejections of (+-)2-amino,5-phosphonopentanoic acid (AP-5), a specific antagonist at NMDA receptors, markedly regularized the firing pattern by reducing the occurrence of bursts (n = 52). In addition, iontophoretic ejections of NMDA, but not kainate or quisqualate, elicited a discharge of these dopamine neurons in bursts (n = 20, 12 and 14, respectively). These data suggest that burst-firing of midbrain dopamine neurons in vivo results from the tonic activation of NMDA receptors by endogenous excitatory amino acids. In view of the critical dependency of catecholamine release on the discharge pattern of source neurons, excitatory amino acid inputs to midbrain dopamine neurons may constitute a major physiological substrate in the control of the dopamine level in target areas.

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In order to obtain information about physiological and homeostasic responses at the maximal Intensity of Endurance of the 45 min "Square-Wave Endurance Exercise Test" (MIE45), three arterial blood samples were taken: (a) at rest; (b) at the 45th min of the SWEET; (c) after 15 min of recovery, to measure paO2, paCO2, [H+], [Hb], and [lactate] in 14 normal male subjects: four trained (T) six well trained (WT) and four others untrained (U). Total mechanical work (TMW) corresponding to MIE45 was significantly higher (mean +/- SEM) respectively in WT (9.22 +/- 0.65 kJ . kg-1, p less than 0.001), than in T (7.17 +/- 0.18 kJ . kg-1, p less than 0.01) and U subjects (4.44 +/- 0.36, p less than 0.001). Because of this the lactate level, which rose significantly during exercise, differed between U and WT subjects (p less than 0.05). In spite of the exhaustive character of the MIE45, [H+] and paO2 remained within the range of normal values. These results suggest that trained and untrained subjects can be trained with the exhausting MIE45 exercise while maintaining a constant [H+] and paO2 at the 45th min of exercise.