D2-like dopamine receptor activation excites rat dorsal raphe 5-HT neurons in vitro.
The aim of the present study was to investigate the effect of dopamine (DA) on the excitability of dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT) neurons using the patch-clamp technique in brain slices. Bath application of DA (1-300 microM) produced a concentration-dependent membrane depolarization in all 5-HT neurons examined. This effect persisted in the presence of tetrodotoxin (TTX; 1 microM) and low extracellular calcium. Moreover, blockade of ionotropic glutamate receptors with 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 2-amino-5-phosphonopentanoic acid (AP5) did not prevent DA-induced depolarization, indicating that it was mediated by a direct effect of DA on 5-HT neurons. The DA-induced depolarization was not antagonized by selective alpha1-adrenergic receptor antagonists, prazosin and WB 4101, but by a nonselective DA receptor antagonist, haloperidol. In addition, the selective D2-like receptor agonist quinpirole and antagonist sulpiride mimicked and blocked DA-induced depolarization, respectively. These results indicate that DA-induced membrane depolarization in DRN 5-HT neurons is mediated by the activation of D2-like DA receptors. The DA-induced membrane depolarization and inward current were associated with an increase in membrane conductance. Examination of the current-voltage (I-V) relationship for the DA-induced inward current revealed that the amplitude of the current increased with membrane hyperpolarization and reversed polarity at a potential near -15 mV. These data suggest that DA-induced depolarization in DRN 5-HT neurons is not mediated by a decrease in potassium conductance, but most likely by the activation of a nonselective cation current.
Haj-Dahmane
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Research Institute on Addictions, University at Buffalo, SUNY at Buffalo, 1021 Main Street, Buffalo, New York 14203, USA. dahmane@ria.buffalo.edu
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004558:Electric Stimulation; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007473:Ion Channels; D017448:Receptors, Dopamine D2; D012701:Serotonin; D013779:Tetrodotoxin; D004298:Dopamine