The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli

Abstract

Finasteride (FIN) is the prototypical inhibitor of steroid 5α-reductase (5αR), the enzyme that catalyzes the rate-limiting step of the conversion of progesterone and testosterone into their main neuroactive metabolites. FIN is clinically approved for the treatment of benign prostatic hyperplasia and male baldness; while often well-tolerated, FIN has also been shown to cause or exacerbate psychological problems in vulnerable subjects. Evidence on the psychological effects of FIN, however, remains controversial, in view of inconsistent clinical reports. Here, we tested the effects of FIN in a battery of tests aimed at capturing complementary aspects of mood regulation and stress reactivity in rats. FIN reduced exploratory, incentive, prosocial, and risk-taking behavior; furthermore, it decreased stress coping, as revealed by increased immobility in the forced-swim test (FST). This last effect was also observed in female and orchiectomized male rats, suggesting that the mechanism of action of FIN does not primarily reflect changes in gonadal steroids. The effects of FIN on FST responses were associated with a dramatic decrease in corticotropin release hormone (CRH) mRNA and adrenocorticotropic hormone (ACTH) levels. These results suggest that FIN impairs stress reactivity and reduces behavioral activation and impulsive behavior by altering the function of the hypothalamus–pituitary–adrenal (HPA) axis.

The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder

“…Rodents treated with finasteride exhibit reduced reactivity towards both incentive stimuli and stress responses(49), both of which play important roles in substance abuse disorders (50,51). Finasteride reduces risktaking behavior, a behavioral feature typically associated with substance use disorders (49,52,53), and may help reduce pathological gambling (54). Since finasteride is FDA-approved and its side effects and toxicology are well-studied, it may be possible to rapidly initiate clinical trials to test the therapeutic potential of this drug for OUD.…”

The 5α-reductase inhibitor finasteride reduces opioid self-administration

“…Although finasteride is typically used for treating non-neuronal indications, there is evidence to suggest it might also have beneficial effects in the nervous system. In animal models, inhibition of 5αR by finasteride has been shown to improve symptoms caused by pathologies driven by dopamine imbalances 47,48 . Dopamine is a central component of the reward pathways, and increased dopaminergic activity has been linked to drug abuse 49 .…”

“…If these results are translated in humans, repurposing finasteride for the treatment of opioid abuse may be a viable therapeutic strategy to treat OUD. Finasteride was previously found to reduce risk-taking behavior, a behavioral feature typically associated with substance use disorders 48,81,82 . Furthermore, preliminary observations suggest that finasteride may help reduce pathological gambling 83 .…”

Androgens’ Effects across the Lifespan in Men and Animal Models

“…Like all good cooks, who occasionally have memory lapses, I did not include a key naturopathic ingredient in our original formula. We do however hope to have our product patented out and on the market soon, aimed at the target audiences indicated above and hitting targets that are not just based upon ED or consummatory aspects of finasteride syndrome but also will have beneficial aspects of drive and motivation (regulated by dopamine) and impulse control regulated by the inputs on the A8, A9, A10 dopamine cell bodies (GABA, GLUTAMATE), and other drive desire aspects to socialize (oxytoxin) [50].…”