Glutamatergic regulation of basal and stimulus-activated dopamine release in the prefrontal cortex.
The present study was undertaken to determine whether basal and stimulus-activated dopamine release in the prefrontal cortex (PFC) is regulated by glutamatergic afferents to the PFC or the ventral tegmental area (VTA), the primary source of dopamine neurons that innervate the rodent PFC. In awake rats, blockade of NMDA or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors in the VTA, or blockade of AMPA receptors in the PFC, profoundly reduced dopamine release in the PFC, suggesting that the basal output of dopamine neurons projecting to the PFC is under a tonic excitatory control of NMDA and AMPA receptors in the VTA, and AMPA receptors in the PFC. Consistent with previous reports, blockade of cortical NMDA receptors increased dopamine release, suggesting that NMDA receptors in the PFC exert a tonic inhibitory control on dopamine release. Blockade of NMDA or AMPA receptors in the VTA as well as blockade of AMPA receptors in the PFC reduced the dopaminergic response to mild handling, suggesting that activation of glutamate neurotransmission also regulates stimulus-induced increase of dopamine release in the PFC. In the context of brain disorders that may involve cortical dopamine dysfunction, the present findings suggest that abnormal basal or stimulus-activated dopamine neurotransmission in the PFC may be secondary to glutamatergic dysregulation.
Takahata
R
R
Department of Psychiatry, Yale University School of Medicine, VA Medical Center, West Haven, Connecticut 06516, USA.
Moghaddam
B
B
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000187:drug effects / Q000502:physiology*; D006234:Handling, Psychological; D007276:Injections, Intraventricular; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013312:Stress, Physiological; D013777:Tetrazoles / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014851:Wakefulness
D007546:Isoquinolines; D016194:Receptors, N-Methyl-D-Aspartate; D013777:Tetrazoles; D018698:Glutamic Acid; C082309:tezampanel; D015763:2-Amino-5-phosphonovalerate; D004298:Dopamine