ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Substance P (neurokinin 1) receptor antagonists enhance dorsal raphe neuronal activity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 81 citations in OpenAlex.
- Neurokinin receptor antagonists for vasomotor symptoms: from KNDy neurons to clinical translation.Nature reviews. Endocrinology · 2026Review
- The role of dorsal raphe nucleus neuropeptides in reward and aversion.Frontiers in behavioral neuroscience · 2025Review
- Neurokinin-1 receptors in the nucleus accumbens shell influence sensitivity to social defeat stress and stress-induced alcohol consumption in male mice.Addiction neuroscience · 2024Article
- The opioid system in depression.Neuroscience and biobehavioral reviews · 2022Review
- Neurokinin receptors in drug and alcohol addiction.Brain research · 2020Review
- In vivo electrophysiological recordings of the effects of antidepressant drugs.Experimental brain research · 2019Review
- The Hypothalamic-Pituitary-Adrenal Axis and Serotonin Metabolism in Individual Brain Nuclei of Mice with Genetic Disruption of the NK1 Receptor Exposed to Acute Stress.Cellular and molecular neurobiology · 2018Article
- Neurokinin-1 receptor antagonism attenuates neuronal activity triggered by stress-induced reinstatement of alcohol seeking.Neuropharmacology · 2015Article
- Review
- Stress-induced reinstatement of alcohol-seeking in rats is selectively suppressed by the neurokinin 1 (NK1) antagonist L822429.Psychopharmacology · 2011Article
- Receptor-selective agonists induce emesis and Fos expression in the brain and enteric nervous system of the least shrew (Cryptotis parva).Pharmacology, biochemistry, and behavior · 2009Article
- Chronic psychosocial stress in tree shrews: effect of the substance P (NK1 receptor) antagonist L-760735 and clomipramine on endocrine and behavioral parameters.Psychopharmacology · 2005Article
- Corticotropin-releasing factor mRNA and substance P receptor binding in the paraventricular hypothalamic nucleus, central nucleus of the amygdala, and locus coeruleus of Sprague-Dawley rats following restraint-induced stress.Journal of molecular neuroscience : MN · 2005Article
- Substance P receptor antagonists in psychiatry: rationale for development and therapeutic potential.CNS drugs · 2005Review
- Impact of substance P receptor antagonism on the serotonin and norepinephrine systems: relevance to the antidepressant/anxiolytic response.Journal of psychiatry & neuroscience : JPN · 2004Article
- Ionic mechanism of long-lasting discharges of action potentials triggered by membrane hyperpolarization in the medial lateral habenula.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2004Article
- Substance P Acts through local circuits within the rat dorsal raphe nucleus to alter serotonergic neuronal activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2003Article
- Visualization and quantification of neurokinin-1 (NK1) receptors in the human brain.Molecular imaging and biologyArticle
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substance P receptor [neurokinin 1 (NK1] antagonists (SPAs) represent a novel mechanistic approach to antidepressant therapy with comparable clinical efficacy to selective serotonin reuptake inhibitors (SSRIs). Because SSRIs are thought to exert their therapeutic effects by enhancing central serotonergic function, we have examined whether SPAs regulate neuronal activity in the dorsal raphe nucleus (DRN), the main source of serotonergic projections to the forebrain. Using in vivo electrophysiological techniques in the guinea pig, we found that administration of the highly selective NK1 receptor antagonist 1-(5-[[(2R,3S)-2-([(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]oxy)-3-(4-phenyl)morpholin-4-yl]methyl]-2H-1,2,3-triazol-4-yl)-N,N-dimethylmethanamine (L-760735) caused an increase in DRN neuronal firing rate. However, unlike chronic treatment with fluoxetine, there was no detectable 5-HT1A autoreceptor desensitization. In vitro electrophysiological investigation showed that these effects were not mediated by a direct action in the DRN, an observation supported by immunocytochemical analysis that identified the lateral habenula (LHb) as a more likely site of action. Subsequently, we found that local application of L-760735 into the LHb increased firing in the DRN, which, together with our data showing that L-760735 increased metabolic activity in the cingulate cortex, amygdala, LHb, and DRN, indicates that the effects of L-760735 may be mediated by disinhibition of forebrain structures acting via a habenulo raphe projection. These findings support other evidence for an antidepressant profile of SPAs and suggest that regulation of DRN neuronal activity may contribute to their antidepressant mechanism of action but in a manner that is distinct from monoamine reuptake inhibitors.
Indexed as
Identifiers
12196596PMC6757969W2129563030What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.