The interaction between finasteride and corticosterone levels: implications for depression-, and anxiety-like behavior and hippocampal synaptic plasticity in male rats
Psychopharmacology (Berl). 2025 May 16. doi: 10.1007/s00213-025-06810-1. Online ahead of print.
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.
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