Jacek Wróbel, Daniel Krzysztof Wójcik, Mark Jeremy Hunt
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引用次数: 0
Abstract
Rationale: NMDA receptor antagonists, used to model psychotic-like states and treat depression, enhance the power of high-frequency oscillations (HFO) in many mammalian brain regions. In rodents, the olfactory bulb (OB) is a particularly important site for generating this rhythm. OB projection neurons express D1 and D2 receptors (D1R and D2R) which interact with NMDA receptors.
Objectives: The aim of this study was to explore the effect of dopamine (DA) signalling in the OB on MK801-enhanced HFO.
Methods: Local field potentials from the OB and locomotor activity were recorded in adult male freely moving rats. MK801 was injected systemically or infused locally to the OB. The effects of D1R and D2R agonists (SKF38393, quinpirole) and antagonists (SCH23390, eticlopride), administered systemically or locally to the OB, were examined on MK801-enhanced HFO. Effects of the antipsychotics risperidone and aripiprazole were also examined.
Results: Local infusion of MK801 enhanced HFO power in the OB to levels similar to those observed after systemic injection. Neither systemic nor local blockade of D1R or D2R affected the MK801-enhanced HFO, despite reductions in hyperlocomotion. However, direct (systemic and local) D2R, but not D1R, stimulation caused a short-lasting reduction of MK801-enhanced HFO power and longer lasting reduction in frequency. Risperidone, but not aripiprazole, reduced MK801-enhanced HFO frequency.
Conclusions: These results suggest that NMDA receptor antagonist-enhanced HFO in the OB is generated predominantly independently of DA influence, however exogenous stimulation of D2R can modulate this rhythm. A second, but not third generation antipsychotic reduced HFO frequency.
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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