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

Int J Neuropsychopharmacol. 2008 Aug;11(5):625-39. doi: 10.1017/S1461145707008383. Epub 2008 Jan 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Behavior, Animal / drug effects
  • Brain Chemistry / drug effects
  • Dopamine / deficiency
  • Dopamine / metabolism*
  • Drug Interactions
  • Locus Coeruleus / cytology
  • Locus Coeruleus / drug effects
  • Male
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurotoxins / toxicity*
  • Norepinephrine / deficiency
  • Norepinephrine / metabolism*
  • Raphe Nuclei / cytology
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / deficiency
  • Serotonin / metabolism*
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / drug effects

Substances

  • Neurotoxins
  • Serotonin
  • Dopamine
  • Norepinephrine