Hypotension-induced dopamine release in prefrontal cortex is mediated by local glutamatergic projections at the level of nerve terminals.
In a previous study it was shown that nitroprusside-induced hypotension strongly enhances the release of dopamine (DA) in the prefrontal cortex (PFC). In the present study we have further investigated the mechanism involved in this effect. Glutamate receptor antagonists were infused into the ventral tegmental area (VTA) or PFC, while DA release was measured in the ipsilateral PFC and hypotension was applied by intravenous infusion of nitroprusside. Infusion into the VTA of neither a NMDA receptor antagonist (CPP), nor a non-NMDA antagonist (DNQX) affected the hypotension-induced increase of DA in the PFC. Intracortical infusion of CPP also failed to affect significantly, whereas local infusion of DNQX inhibited the hypotension-enhanced release of DA dose-dependently. The stimulation of DA release was relatively small in the VTA as well as in the nucleus accumbens when compared with the response in the PFC. It is concluded that DA released from mesocortical neurons can be modulated by two different mechanisms: first, by glutamate afferents to the VTA that modify the nerve-impulse flow of DA neurons; and, second, by glutamate afferents to the PFC that act at the level of the DA nerve terminals. The behaviour context (arousal or stress versus hypotension) determines which type of interaction predominates.
Kawahara
Yukie
Y
Department of Biomonitoring and Sensoring, University Center for Pharmacy, University of Groningen, Antonius, The Netherlands. ykawa@farm.rug.nl
Kawahara
Hiroshi
H
Westerink
Ben H C
BH
D000818:Animals; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D018698:Glutamic Acid / Q000378:metabolism*; D006234:Handling, Psychological; D007022:Hypotension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009599:Nitroprusside; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D011810:Quinoxalines; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D009599:Nitroprusside; D018698:Glutamic Acid; C056723:FG 9041; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D004298:Dopamine