5-Hydroxytryptamine and 5-hydroxytryptaminergic-dopaminergic interactions in the ventral tegmental area of rat brain

Beart, Philip M; McDonald, D.

doi:10.1111/j.2042-7158.1982.tb04801.x

Cited by 60 publications

(29 citation statements)

References 21 publications

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“…3 H]DA in VTA slices (Beart and McDonald, 1982). In line with these results, microinfusion of 5-HT in the VTA increased DA release in projection areas such as the nucleus accumbens (Guan and McBride, 1989).…”

Section: Reciprocal Interactions Between Da and 5-ht Neuronssupporting

confidence: 74%

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

Guiard

Mansari

Merali

et al. 2008

International Journal of Neuropsychopharmacology

262

143

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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.

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Section: Reciprocal Interactions Between Da and 5-ht Neuronssupporting

confidence: 74%

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

Guiard

Mansari

Merali

et al. 2008

International Journal of Neuropsychopharmacology

262

143

View full text Add to dashboard Cite

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“…The cell bodies and terminal regions of all three DA pathways are innervated by 5-HT neurons originating in the medial and dorsal raphe nuclei (Geyer et al, 1976;Parent et al, 1981;Beart and McDonald, 1982;Nedergaard et al, 1988). Studies show that there are direct synaptic contacts between 5-HT terminals and DA cells in the midbrain (Herve et al, 1987;Nedergaard et al, 1988).…”

Section: Da Systemsmentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

537

311

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The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

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“…Both the mPFC and VTA are innervated by serotonergic neurons originating in the dorsal raphe (Azmitia and Segal, 1978;Beart and McDonald, 1982). Immunohistochemical studies indicate the presence of 5-HT2A receptors in both the PFC (Willins et al, 1997;Jakab and Goldman-Rakic, 1998;Miner et al, 2003) and VTA (Doherty and Pickel, 2000;Nocjar et al, 2002) where they could, at least in theory, modulate DA neuronal activity.…”

Section: Introductionmentioning

confidence: 99%

Evidence for the Preferential Involvement of 5-HT2A Serotonin Receptors in Stress- and Drug-Induced Dopamine Release in the Rat Medial Prefrontal Cortex

Pehek

Nocjar

Roth

et al. 2005

Neuropsychopharmacol

175

104

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The mechanism(s) by which serotonin modulates dopamine release in the medial prefrontal cortex is not known, although studies suggest an involvement of 5-HT2 family receptors. We employed in vivo microdialysis and putatively selective 5-HT2A antagonists (M100907, MDL 11,939, SR46349B) to determine if 5-HT2A receptors are responsible for both drug-and stress-induced DA release in the medial prefrontal cortex. MDL 11,939 and SR46349B receptor-binding studies indicated, for the first time, that only MDL 11,939 had greater selectivity for the 5-HT2A vs the 5-HT2C receptor subtypes similar to M100907, and that both showed low or no affinity for non-5-HT2 receptors. Reverse dialysis with 5-HT2A antagonists had little or no effect on basal dopamine efflux. However, intracortical administration of MDL 11,939 or M100907 attenuated dopamine release induced by systemic administration of the 5-HT2 agonist DOI. Dual-probe microdialysis demonstrated that systemic DOI also increased glutamate concentrations in the ventral tegmental area (VTA). This was blocked by intracortical M100907. Cortical perfusion with M100907, or the atypical antipsychotic drug risperidone, but not the 5-HT2B/C ligand SB 206553, also decreased dopamine release induced physiologically by stress. These results indicate that stimulation of cortical 5-HT2A receptors increases the release of dopamine from the mesocortical system. They suggest that this effect may be mediated by increases in glutamate release from corticotegmental projections to the VTA. Additionally, they indicate that cortical 5-HT2A receptors modulate evoked dopamine release, such as that observed physiologically following mild stress. These findings may have implications for the pharmacological treatment of disorders resulting from or exacerbated by stress.

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5-Hydroxytryptamine and 5-hydroxytryptaminergic-dopaminergic interactions in the ventral tegmental area of rat brain

Cited by 60 publications

References 21 publications

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

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

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Evidence for the Preferential Involvement of 5-HT2A Serotonin Receptors in Stress- and Drug-Induced Dopamine Release in the Rat Medial Prefrontal Cortex

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