Dopamine desynchronizes the pace-making neuronal activity of rat respiratory rhythm generation.
In an excised Wistar rat medulla-spinal cord block preparation we previously found that dopamine slows respiratory rhythm by activation of dopamine D(4) receptors [Fujii et al., (2004)Neurosci. Res., 50, 355-359.] In the present paper, we investigated the effect of dopamine on pre-inspiratory (Pre-I) and inspiratory (I) neurons using the combination of an optical recording technique with a voltage-sensitive dye, unit recording and patch-clamp recording. Optical imaging of the ventral surface of the block preparation disclosed different locations and activity patterns of Pre-I and I neurons. In addition to slowing the rhythm, dopamine depressed respiratory activity of Pre-I neurons collectively but not that of I neurons. The dopaminergic suppression of Pre-I neurons was mimicked by a dopamine D(4) receptor agonist, PD168077. Unit recording and patch-clamp recording demonstrated that dopamine depolarizes Pre-I neurons, disperses Pre-I firing and depresses Pre-I phase postsynaptic potentials (PSPs) of I neurons. Immunohistological investigation revealed that Pre-I neurons express dopamine D(4) receptors. We found that approximately 60% of Pre-I neurons express dopamine D(4) receptors. These results show that dopaminergic respiratory rhythm depression is due to dispersion of synchronized Pre-I driving of I neurons caused by dopamine D(4) receptor stimulation of Pre-I neurons.
Fujii
Morimitsu
M
Laboratory for Memory and Learning, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Umezawa
Kazuo
K
Arata
Akiko
A
D000818:Animals; D000831:Animals, Newborn; D001549:Benzamides / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000166:cytology*; D008959:Models, Neurological; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D050638:Receptors, Dopamine D4 / Q000378:metabolism; D012119:Respiration / Q000187:drug effects*; D015656:Respiratory Mechanics / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D001549:Benzamides; D018491:Dopamine Agonists; C477501:N-((4-(2-cyanophenyl)-1-piperazinyl)methyl)-3-methylbenzamide; D010879:Piperazines; D050638:Receptors, Dopamine D4; D013779:Tetrodotoxin; D004298:Dopamine