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.
Electroanalytical techniques for the in vivo measurement of neurotransmitters in brain tissue have been applied especially to the catecholamines, which are easily oxidizable. Measurements are, however, complicated by the presence of ascorbic acid (AA) in brain tissue. Lane et al. have been able to circumvent this problem, at least in part, by the application of differential pulse voltametry (DPV) to a surface-modified platinum electrode, obtaining distinct oxidation current peaks in recordings from the rat neostriatum which are attributed to AA and to dopamine (DA), respectively, but which are also unstable. We have recently described a new type of electrode, consisting of a pyrolytic carbon fibre 8 micrometers thick and 0.5 mm long. We now report that the DPV method used in conjunction with an electrochemical treatment of this electrode yields stable and reproducible peaks in which catecholamines and AA are resolved from each other. Moreover, pharmacological investigations suggest that the catecholamine peak measured in vivo in the rat neostriatum should be attributed to 3, 4-dihydroxyphenylacetic acid (DOPAC), suggesting that our technique may be a useful means of following dopaminergic activity in vivo.
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