Letícia R Pinheiro, Alana T Frias, Luis Gustavo A Patrone, Kênia C Bícego, Hélio Zangrossi, Luciane H Gargaglioni
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引用次数: 0
Abstract
Rationale: There is a connection between respiratory pathologies and panic disorder, since episodes of hypercapnia can trigger anxiety-related behaviors. The locus coeruleus (LC) is a CO2/pH chemosensitive region capable of generating emotional and physical responses during stress episodes. The acid-sensitive ion channel type 1a (ASIC1a) participates in the panicogenic response induced by CO2.
Objectives: Our study investigated the role of ASIC1a channels in the LC in detecting hypercapnic acidosis and their participation in the respiratory and behavioral responses induced by CO2.
Methods: We tested the effects of injection of an ASIC1a antagonist [Psalmotoxin-1 (Pstx-1-50 ng/0.1uL)] into the LC of C57BL/6 male and female mice on respiratory, metabolic, and behavioral responses to 20% CO2. To assess the role of ASIC1a channels in basal activity and CO2 chemosensitivity of LC neurons, whole-cell patch-clamp recordings were performed on brainstem slices from male mice using Pstx-1 (0.050 µg/mL).
Results: Pstx-1 intra-LC did not change ventilation and metabolism under normocapnic and hypercapnic conditions in both male and female mice. As to CO2-behavioral responses, Pstx-1 injection decreased the number of jumps in males, but there was no significant difference in females. In vitro, Pstx-1 reduced the activity of LC chemoreceptors under hypercapnia in males, but no change was observed under control conditions.
Conclusions: ASIC1a channels in the LC do not participate in respiratory control under normocapnia and hypercapnia, but are involved in CO2-induced panic behavior, demonstrating a sex-dependent response. Furthermore, ASIC1a channels contribute to the CO2 chemosensitivity of LC neurons in males.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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