The activation of D2-like dopamine receptors increases NMDA currents in the dorsal raphe serotonergic neurons

Neurosci Lett. 2024 Sep 14:839:137933. doi: 10.1016/j.neulet.2024.137933. Epub 2024 Aug 12.

Abstract

The dorsal raphe nucleus (DRN) receives dopaminergic inputs from the ventral tegmental area (VTA). Also, the DRN contains a small population of cells that express dopamine (DRNDA neurons). However, the physiological role of dopamine (DA) in the DRN and its interaction with serotonergic (5-HT) neurons is poorly understood. Several works have reported moderate levels of D1, D2, and D3 DA receptors in the DRN. Furthermore, it was found that the activation of D2 receptors increased the firing of putative 5-HT neurons. Other studies have reported that D1 and D2 dopamine receptors can interact with glutamate NMDA receptors, modulating the excitability of different cell types. In the present work, we used immunocytochemical techniques to determine the kind of DA receptors in the DRN. Additionally, we performed electrophysiological experiments in brainstem slices to study the effect of DA agonists on NMDA-elicited currents recorded from identified 5-HT DRN neurons. We found that D2 and D3 but not D1 receptors are present in this nucleus. Also, we demonstrated that the activation of D2-like receptors increases NMDA-elicited currents in 5-HT neurons through a mechanism involving phospholipase C (PLC) and protein kinase C (PKC) enzymes. Possible physiological implications related to the sleep-wake cycle are discussed.

Keywords: Dopamine receptors; Dorsal raphe neurons; NMDA currents; Serotonin neurons.

MeSH terms

  • Animals
  • Dopamine Agonists / pharmacology
  • Dorsal Raphe Nucleus* / drug effects
  • Dorsal Raphe Nucleus* / metabolism
  • Male
  • N-Methylaspartate / metabolism
  • N-Methylaspartate / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2* / metabolism
  • Receptors, Dopamine D3 / metabolism
  • Receptors, N-Methyl-D-Aspartate* / metabolism
  • Serotonergic Neurons* / drug effects
  • Serotonergic Neurons* / metabolism
  • Serotonergic Neurons* / physiology
  • Type C Phospholipases / metabolism

Substances

  • Receptors, Dopamine D2
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Dopamine D3
  • N-Methylaspartate
  • Receptors, Dopamine D1
  • Dopamine Agonists
  • Type C Phospholipases
  • Drd3 protein, rat