ReviewSerotonergic modulation of the limbic system
Section snippets
Overview
The limbic system is composed of cortical as well as subcortical structures, which are intimately interconnected. The major structures of the limbic system include prefrontal cortex, cingulate cortex, entorhinal cortex, hippocampus, nucleus accumbens (ventral striatum), ventral pallidum, amygdala, and anterior hypothalamus (see Swanson and Petrovich, 1998, Kandel et al., 2000, Heimer, 2003). Connections between these structures form complex circuits. Furthermore, projections between structures
Two distinct central serotonergic systems
Serotonin-containing neuronal cell bodies are restricted to discrete groups of cells or nuclei located along the midline of the brainstem. Their axonal projections, however, innervate nearly every area of the central nervous system. Dahlström and Fuxe (1964), using the Falck–Hillarp technique of histofluorescence, observed that the majority of serotonergic soma were found in cell body groups previously designated by Taber et al. (1960) as the raphe nuclei based on cytoarchitectural criteria,
Ascending serotonergic projections to limbic structures
The dorsal periventricular path and the ventral tegmental radiations are the two main ascending serotonergic pathways from the midbrain raphe nuclei to the forebrain. Both pathways converge in the caudal hypothalamus where they join the medial forebrain bundle and axons of dopaminergic (A8, A9, A10) and noradrenergic (A6) cell body groups (Moore et al., 1978, Parent et al., 1981; see also Molliver, 1987, Vertes, 1991).
The dorsal and median raphe nuclei give rise to distinct serotonergic
Volume transmission
The action of neurotransmitters may be restricted to the synaptic cleft, specifically referred to as hard-wired neurotransmission, or may require that the neurotransmitter diffuse to remote receptor sites, referred to as diffuse, volume or paracrine transmission. Important factors determining the type of neurotransmission include the location of receptors with respect to release sites, the amount of neurotransmitter released, rate of diffusion away from the release site, and the removal or
Disorders of limbic system and treatment strategies
In humans, disorders associated with dysfunction within the limbic system include schizophrenia, major depression, and anxiety disorders. Drugs used in the treatment of these disorders modulate or alter serotonergic neurotransmission (see Jones and Blackburn, 2002).
Some considerations in the treatment of disorders of the limbic system
Serotonergic projections from the dorsal and median raphe differ in the topographical organization and density of their respective innervation of forebrain structures. With regard to the treatment of affective disorders, i.e. major depression and anxiety disorders, it is an intriguing possibility that these two distinct serotonergic systems are differentially modulated by drugs that block serotonin reuptake (e.g. tricyclic antidepressants and selective serotonin reuptake inhibitors). Indeed,
Acknowledgements
This work was supported by US PHS grants MH 52369 and funds from the National Association for Research on Schizophrenia and Depression (NARSAD).
References (84)
- et al.
Serotonin model of schizophrenia: emerging role of glutamate mechanisms
Brain Res. Rev.
(2000) - et al.
New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia innominata
Neuroscience
(1988) - et al.
How does pindolol improve antidepressant action?
Trends Pharmacol. Sci.
(2001) - et al.
A review of central 5-HT receptors and their function
Neuropharmacology
(1999) - et al.
Quantitative data on serotonin nerve terminals in adult rat neocortex
Brain Res.
(1976) - et al.
Correspondence between 5-HT2 receptors and serotonergic axons in rat neocortex
Brain Res.
(1988) - et al.
Effect of chronic antidepressant treatment on 5-HT1B presynaptic heteroreceptors inhibiting acetylcholine release
Neuropharmacology
(1994) - et al.
Electrophysiologically-identified serotonin receptors in the rat CNS. Effect of antidepressant treatment
Neuropharmacology
(1984) - et al.
Ultrastructural evidence for diffuse transmission by monoamine and acetylcholine neurons of the central nervous system
Prog. Brain Res.
(2000) - et al.
Serotonin nerve terminals in adult rat neocortex
Brain Res.
(1975)
Monoaminergic innervation of the macaque extended amygdala
Neuroscience
Fluoxetine enantiomers as antagonists of p-chloroamphetamine effects in rats
Pharmacol. Biochem. Behav.
Histologic and enzymatic studies of the mesolimbic and neostriatal serotonergic pathways
Brain Res.
The medial prefrontal cortex in the rat: evidence for a dorso-ventral distinction based upon functional and anatomical characteristics
Neurosci. Biobehav. Rev.
The putative 5-HT1B receptor agonist CP-93,129 suppresses rat hippocampal serotonin release in vivo: comparison with RU24969
Eur. J. Pharmacol.
Relationships of 5-hydroxytryptamine immunoreactive terminal-like varicosities to 5-hydroxytryptamine-2A receptor-immunoreactive neuronal processes in the rat forebrain
J. Chem. Neuroanat.
The medical benefit of 5-HT research
Pharmacol. Biochem. Behav.
Immunocytochemical and elctron microscopic studiy of serotonin neuronal organization in the dorsal raphe nucleus of the monkey
Neuroscience
Origins of serotonin innervation of forebrain structures
Exp. Neurol.
Distinguishing characteristics of serotonin and non-serotonin-containing cells in the dorsal raphe nucleus: electrophysiological and immunohistochemical studies
Neuroscience
Identification of serotonin and non-serotonin-containing neurons of the mid-brain raphe projecting to the entorhinal area and the hippocampal formation. A combined immunohistochemical and fluorescent retrograde tracing study in the rat
Neuroscience
Evidence for dual serotonergic projections to neocortex: axons from the dorsal and median raphe nuclei are differentially vulnerable to the neurotoxin p-chloroamphetamine (PCA)
Exp. Neurol.
Cholinergic terminals in rat hippocampus possess 5-HT1B receptors mediating inhibition of acetylcholine release
Eur. J. Pharmacol.
Serotonin receptors: their key role in drugs to treat schizophrenia
Prog. Neuropsychopharmacol. Biol. Psychiatry
Serotonergic afferents to the dorsal raphe nucleus: evidence from HRP and synaptosomal uptake studies
Brain Res.
Organization of raphe-cortical projections in rat: a quantitative retrograde study
Brain Res. Bull.
Quantified distribution of the serotonin innervation in adult rat hippocampus
Neuroscience
Ultrastructural features of the serotonin innervation in adult rat hippocampus: an immunocytochemical description in single and serial thin sections
Neuroscience
Organization of ascending serotonin neurons in the adult rat brain. A radioautographic study after intraventricular administration of [3H]5-hydroxytryptamine
Neuroscience
The monoaminergic innervation of the amygdala in the squirrel monkey: an immunocytochemical study
Neuroscience
Serotonin innervation in adult rat neostriatum. II. Ultrastructural features: a radioautographic and immunocytochemical study
Brain Res.
Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons
Neuropharmacology
Distribution of serotonin-immunoreactivity in the central nervous system of the rat- cell bodies and terminals
Neuroscience
What is the amygdala?
Trends Neurosci.
Species differences in the projections from the entorhinal cortex to the hippocampus
Brain Res. Bull.
The organization of serotonergic projections to cerebral cortex in primates: regional distribution of axon terminals
Neuroscience
Electrophysiology of the central serotonin system: receptor subtypes and transducer mechanisms
Ann. NY Acad. Sci.
Pindolol induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors
Arch. Gen. Psychiatry
Quantified regional and laminar distribution of the serotonin innervation in the anterior half of adult rat cerebral cortex
J. Chem. Neuroanat.
Median and dorsal raphe neurons are not electrophysiologically identical
J. Neurophysiol.
Possible neurobiological mechanisms underlying faster onset of antidepressant action
J. Clin. Psychiatry
Dual serotonin (5-HT) projections to the nucleus accumbens core and shell: relation of the 5-HT transporter to amphetamine-induced neurotoxicity
J. Neurosci.
Cited by (236)
5-HT1A receptors within the intermediate lateral septum modulate stress vulnerability in male mice
2024, Progress in Neuro-Psychopharmacology and Biological PsychiatryEffects of olanzapine on hippocampal CA3 and the prefrontal cortex local field potentials
2024, European Journal of Pharmacology5-HT1A receptor in the central amygdala and 5-HT2A receptor in the basolateral amygdala are involved in social hierarchy in male mice
2023, European Journal of PharmacologySerotonergic mediation of the brain-wide neurogenesis: Region-dependent and receptor-type specific roles on neurogenic cellular transformation
2023, Current Research in NeurobiologyMDMA related neuro-inflammation and adenosine receptors
2022, Neurochemistry InternationalCitation Excerpt :Even though MDMA defined as a substances with no currently accepted medical use and a high potential for abuse, the use of that in many societies seems to be expanding. The United Nations has estimated that the consumption of ecstasy around the world has affected 12 million peoples (Hensler 2006). In the United States, ecstasy use reportedly increased significantly during the 1990s and early 2000s (Koesters et al., 2002).