D2-like dopamine receptor activation excites rat dorsal raphe 5-HT neurons in vitro

Eur J Neurosci. 2001 Jul;14(1):125-34. doi: 10.1046/j.0953-816x.2001.01616.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Dopamine / metabolism
  • Dopamine / pharmacology*
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / pharmacology
  • Dopamine D2 Receptor Antagonists
  • Electric Stimulation
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Male
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Raphe Nuclei / cytology
  • Raphe Nuclei / drug effects*
  • Raphe Nuclei / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / agonists*
  • Receptors, Dopamine D2 / metabolism
  • Serotonin / metabolism*
  • Tetrodotoxin / pharmacology


  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Dopamine Agonists
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Ion Channels
  • Receptors, Dopamine D2
  • Serotonin
  • Tetrodotoxin
  • Dopamine