Dopamine D1 and D2 receptor antagonism differentially modulates stimulation of striatal neurotransmitter levels by N-methyl-D-aspartic acid.
The effects of local perfusion with the dopamine D1 receptor antagonist SCH 23390 and the dopamine D2 receptor antagonist raclopride on basal and N-methyl-D-aspartate (NMDA) stimulated dopamine, gamma-aminobutyric acid (GABA) and glutamate levels in the dorsolateral striatum were monitored using in vivo microdialysis in the halothane anaesthetized rat. Local perfusion (90 min) with SCH 23390 and raclopride (1 and 10 microM) dose dependently increased basal striatal dopamine release whereas GABA and glutamate dialysate levels were unaffected. Local perfusion (10 min) with the 1 mM concentration of NMDA increased striatal dopamine, GABA and glutamate outflow. However, when perfused together with SCH 23390 (1 microM) NMDA inhibited glutamate efflux. Moreover, in the presence of SCH 23390 (10 microM) the NMDA induced rise in dopamine and GABA levels was partly prevented. On the other hand, raclopride 1 microM enhanced the NMDA stimulated GABA efflux while at 10 microM it partly counteracted the NMDA induced dopamine release. These data demonstrate that NMDA induced changes in striatal neurotransmitter outflow are effectively modified by dopamine D1 and D2 receptor blockade.
Morari
M
M
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
O'Connor
W T
WT
Ungerstedt
U
U
Fuxe
K
K
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012457:Salicylamides / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D005971:Glutamates; D018377:Neurotransmitter Agents; D017447:Receptors, Dopamine D1; D012457:Salicylamides; D018698:Glutamic Acid; D020891:Raclopride; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D004298:Dopamine