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

Full 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.

Author information

Author/s: Guiard, Bruno P (BP); El Mansari, Mostafa (M); Merali, Zul (Z); Blier, Pierre (P);

Affiliation: Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada. bguiard(-atsign-)rohcg.on.ca

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) (Int J Neuropsychopharmacol), published in England. (Language: eng)

Reference: 2008-Aug; vol 11 (issue 5) : pp 625-39

Dates: Created 2008/07/02; Completed 2008/09/24;

PMID: 18205979, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

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