The interaction between finasteride and corticosterone levels: implications for depression-, and anxiety-like behavior and hippocampal synaptic plasticity in male rats.
Jose Nayana, Byrathnahalli S Shankaranarayana Rao, Bettadapura N Srikumar
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引用次数: 0
Abstract
Rationale: Finasteride is FDA-approved for the treatment of hair loss and in older men for benign prostatic hyperplasia. However, some patients treated with finasteride reported suicidal ideation, depression, and anxiety. The neurobiological mechanisms underlying this are not clearly understood. Previously, we showed that short-term finasteride administration results in depression- and anxiety-like behaviour. Since finasteride treatment is long-term in the clinic, we examine the effects of chronic finasteride administration in the current study.
Objective: This study aims to understand the behavioral, cellular, and molecular changes in male rats following 21 days of finasteride (3 mg, 10 mg, and 30 mg/Kg) administration.
Methods: Depression-like behavior was evaluated using forced swim (FST), sucrose preference (SPT), and splash tests. Anxiety-like behavior was assessed using elevated plus maze (EPM), open field (OFT), light-dark (LDT), Vogel's conflict (VCT), and home cage emergence (HCET), and depression-related anxiety in novelty-suppressed feeding task (NSFT) tests. Hippocampal synaptic plasticity was assessed by field excitatory post-synaptic potentials (fEPSP) recordings in the Schaffer-collateral-CA1 synapses, and plasma corticosterone levels were estimated using ELISA.
Results: Chronic finasteride administration induced depression-like and anxiety-like behavior in SPT and EPM, respectively, but not in the other paradigms. There was a modest decrease in long-term potentiation in the hippocampus. Interestingly, there was an increase in the plasma corticosterone levels with 6 days of finasteride administration, but not after 14 or 21 days of administration.
Conclusions: Chronic administration of finasteride did not induce a robust depression- and anxiety-like behavior and modestly affected synaptic plasticity. This could be potentially because of the adaptive response observed in the plasma corticosterone levels.
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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