Functional interactions between dopamine, serotonin and norepinephrine neurons: An in-vivo electrophysiological study in rats with monoaminergic lesions

Bruno P. Guiard, Mostafa El Mansari, Zul Merali, Pierre Blier

Research output: Contribution to journalArticlepeer-review

225 Citations (Scopus)

Abstract

Anatomical studies have established the existence of reciprocal relationships between the main population of monoamine, serotonin (5-HT), norepinephrine (NE) and dopamine (DA) neurons in the brain. The present study was thus conducted to examine the firing activity of 5-HT and NE neurons in DA-depleted rats, as well as the firing activity of DA neurons in 5-HT- or NE-depleted rats. The selective lesion of DA neurons elicited by 6-hydroxydopamine (6-OHDA) decreased the spontaneous firing activity of dorsal raphe (DR) nucleus 5-HT neurons by 60%, thus revealing the excitatory effect of the DA input on these 5-HT neurons. In contrast, the selective lesion of 5-HT neurons produced by 5,7-dihydroxytryptamine (5,7-DHT) enhanced by 36% the firing activity of VTA DA neurons, thereby indicating an inhibitory effect of the 5-HT input on these DA neurons. With regard to the reciprocal interaction between DA and NE neurons, it was observed that the selective loss of DA neurons achieved by the intra-ventral tegmental area (VTA) injection of 6-OHDA increased the firing activity of a subset of locus coeruleus (LC) NE neurons by 47%. The selective loss of NE neurons in response to the intra-LC injection of 6-OHDA enhanced the firing activity of VTA DA neurons by 70%, demonstrating a net inhibitory role of the NE input on VTA DA neurons. These findings have important consequences for antidepressant treatments aimed at enhancing simultaneously 5-HT, NE and DA transmission. Indeed, based on the understanding of such interactions, it may be possible to develop strategies to improve the effectiveness of antidepressant drugs by preventing counter-productive negative feedback actions.

Original languageEnglish
Pages (from-to)625-639
Number of pages15
JournalInternational Journal of Neuropsychopharmacology
Volume11
Issue number5
DOIs
Publication statusPublished - Aug 2008
Externally publishedYes

Keywords

  • Antidepressants
  • Dopamine
  • Firing activity
  • Norepinephrine
  • Serotonin

Fingerprint

Dive into the research topics of 'Functional interactions between dopamine, serotonin and norepinephrine neurons: An in-vivo electrophysiological study in rats with monoaminergic lesions'. Together they form a unique fingerprint.

Cite this