N-methyl-D-aspartic acid differentially regulates extracellular dopamine, GABA, and glutamate levels in the dorsolateral neostriatum of the halothane-anesthetized rat: an in vivo microdialysis study.
The effects of local perfusion with the glutamate receptor agonist NMDA and the noncompetitive NMDA receptor antagonist dizolcipine (MK-801) on extracellular dopamine (DA), GABA, and glutamate (Glu) levels in the dorsolateral striatum were monitored using in vivo microdialysis in the halothane-anesthetized rat. In addition, the sensitivity of both the basal and NMDA-induced increases in levels of these neurotransmitter substances to perfusion with tetrodotoxin (TTX: 10(-5) M) and a low Ca2+ concentration (0.1 mM) was studied. The results show that the local perfusion (10 min) with both the 10(-3) and 10(-4) M dose of NMDA increased striatal DA and GABA outflow, whereas only the (10(-3) M) dose of NMDA was associated with a small and delayed increase in extracellular Glu levels. The NMDA-induced effects were dose-dependently counteracted by simultaneous perfusion with MK-801 (10(-6) and 10(-5) M). Both the basal and NMDA (10(-3) M)-induced increase in extracellular striatal DA content was reduced in the presence of TTX and a low Ca2+ concentration, whereas both basal and NMDA-stimulated GABA levels were unaffected by these treatments. Both the basal and NMDA-stimulated Glu levels were enhanced following TTX treatment, whereas perfusion with a low Ca2+ concentration reduced basal Glu levels and enhanced and prolonged the NMDA-induced stimulation. These data support the view that NMDA receptor stimulation plays a role in the regulation of extracellular DA, GABA, and Glu levels in the dorso-lateral neostriatum and provide evidence for a differential effect of NMDA receptor stimulation on these three striatal neurotransmitter systems, possibly reflecting direct and indirect actions mediated via striatal NMDA receptors.
Morari
M
M
Department of Histology, Karolinska Institutet, Stockholm, Sweden.
O'Connor
W T
WT
Ungerstedt
U
U
Fuxe
K
K
D000758:Anesthesia; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006221:Halothane; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005971:Glutamates; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D006221:Halothane; D004298:Dopamine