Serotonin 5-HT1A Receptors as Targets for Agents to Treat Psychiatric Disorders: Rationale and Current Status of Research

Celada, Pau; Bortolozzi, Analı́a; Artigas, Francesc

doi:10.1007/s40263-013-0071-0

Cited by 259 publications

(190 citation statements)

References 193 publications

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“…Thus, a potential mechanism is that OT provokes the release of serotonin, which in turn changes 5-HT 1A R functioning. This finding can have an important impact for pharmaceutic research, as OT, 5-HT 1A R, and SERT are all important targets in several pathologies, including depression, autism, and general anxiety (Bandelow et al, 2002;Celada et al, 2013;Vasa et al, 2014). Thus, studying the interaction between these systems could be a critical step toward improved psychiatric treatments.…”

Section: Limitationsmentioning

confidence: 99%

“…We have recently confirmed in humans the existence of OT/5-HT interactions in brain in regions important for social cognition and emotions, notably in the amygdala, hippocampus, dorsal raphe nucleus (DRN), insula, and orbitofrontal cortex (OFC) using PET neuroimaging (Mottolese et al, 2014). A better understanding of such interactions could have important implications for clinical research as 5-HT is also a current therapeutic target for different psychiatric diseases (Bandelow et al, 2002;Celada et al, 2013;Vasa et al, 2014). In our study, intranasal OT administration increased 2Ј-Methoxyphenyl-(N-2Ј-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine ([ 18 F]MPPF) (a serotonin 1A receptor [5-HT 1A R] radiotracer) nondisplaceable binding potential (BP ND ), which suggests either a decreased serotonin concentration or an increased availability of 5-HT 1A receptors.…”

Section: Introductionmentioning

confidence: 99%

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Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate

et al. 2017

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Oxytocin (OT) is increasingly studied for its therapeutic potential in psychiatric disorders, which are associated with the deregulation of several neurotransmission systems. Studies in rodents demonstrated that the interaction between OT and serotonin (5-HT) is critical for several aspects of social behavior. Using PET scan in humans, we have recently found that 5-HT 1A receptor (5-HT 1A R) function is modified after intranasal oxytocin intake. However, the underlying mechanism between OT and 5-HT remains unclear. To understand this interaction, we tested 3 male macaque monkeys using both

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Section: Limitationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate

et al. 2017

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“…They are expressed on serotonergic neurons in the raphe, where they exert autoinhibitory function, and various other brain areas involved in fear and anxiety [54,55]. Mechanisms underlying the anxiolytic effects of 5-HT 1A R activation are complex, varying between both brain region, and pre-versus postsynaptic locus, and are not fully established [56]. While in vitro studies suggest CBD acts as a direct 5-HT 1A R agonist [57], in vivo studies are more consistent with CBD acting as an allosteric modulator, or facilitator of 5-HT 1A signaling [58].…”

Section: -Ht 1a Receptorsmentioning

confidence: 99%

Cannabidiol as a Potential Treatment for Anxiety Disorders

et al. 2015

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Cannabidiol (CBD), a Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a range of neuropsychiatric disorders. The purpose of the current review is to determine CBD's potential as a treatment for anxiety-related disorders, by assessing evidence from preclinical, human experimental, clinical, and epidemiological studies. We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely; however, few studies have investigated chronic CBD dosing. Likewise, evidence from human studies supports an anxiolytic role of CBD, but is currently limited to acute dosing, also with few studies in clinical populations. Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with need for further study of chronic and therapeutic effects in relevant clinical populations.

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“…The SERT is but one of the several regulators of 5-HT Ext (Celada et al, 2013;Daws, 2009;Sharp et al, 2007;Uutela et al, 2009). Selectively blocking the SERT might not always elevate 5-HT Ext enough to elicit maximal antidepressant response.…”

Section: Introductionmentioning

confidence: 99%

SSRI Augmentation by 5-Hydroxytryptophan Slow Release: Mouse Pharmacodynamic Proof of Concept

Jacobsen

Rudder

Roberts

et al. 2016

Neuropsychopharmacol

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Drugs, notably SSRIs, that elevate brain extracellular 5-HT (5-HT Ext ) are antidepressants. Unfortunately, most patients fail to remit. Multipronged clinical evidence suggests that elevating 5-HT Ext beyond the SSRI effect enhances antidepressant efficacy, but previous such drug strategies had prohibitive limitations. In humans, adjunct treatment with the 5-HT precursor 5-hydroxytryptophan (5-HTP) elevates 5-HT Ext beyond the SSRI effect. Small pilot trials suggest that adjunct 5-HTP can confer antidepressant response in treatment-resistant depression (TRD). However, sustained, stable 5-HT Ext elevation is required for antidepressant effect; therefore, the rapid absorption and elimination of standard 5-HTP immediate release (IR) likely curtail 5-HTP IR's antidepressant potential. Slow-release (SR) drug delivery can crucially improve efficacy and safety of rapidly absorbed and eliminated compounds. Here we tested in mice the hypothesis that SR delivery will substantially improve 5-HTP's drug properties, by minimizing adverse effects and securing sustained 5-HT Ext elevation beyond the SSRI effect. We modeled 5-HTP SR with minipumps, 5-HTP IR with injections, and chronic SSRI with dietary fluoxetine. We tested adjunct 5-HTP SR in wild-type mice and in mice with low brain 5-HT owing to expression of a mutant form of the brain 5-HT synthesis enzyme, tryptophan hydroxylase 2. In both lines of mice, adjunct 5-HTP SR synergized with SSRI to elevate 5-HT Ext beyond the SSRI effect. We observed no adverse effect. Adjunct 5-HTP IR could not produce this therapy-like profile, producing transient 5-HT Ext spikes and marked adverse effects. Integrated with a body of clinical data, our mouse data suggest that an adjunct 5-HTP SR drug could safely and effectively elevate 5-HT Ext beyond the SSRI effect and represent a novel treatment for TRD.

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Serotonin 5-HT1A Receptors as Targets for Agents to Treat Psychiatric Disorders: Rationale and Current Status of Research

Cited by 259 publications

References 193 publications

Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate

Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate

Cannabidiol as a Potential Treatment for Anxiety Disorders

SSRI Augmentation by 5-Hydroxytryptophan Slow Release: Mouse Pharmacodynamic Proof of Concept

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