Identifying fast-onset antidepressants using rodent models.

Area of Science:

• Neuroscience
• Pharmacology
• Psychiatry

Background:

• Depression is a leading global cause of disability and suicide.
• Classical antidepressants have a 2-4 week delay in therapeutic effect, increasing suicide risk.
• Fast-onset antidepressants are critically needed.

Purpose of the Study:

• To review and assess the validity of rodent models for detecting antidepressant onset.
• To evaluate the efficacy of existing and novel compounds for fast-acting antidepressant effects.

Main Methods:

• Reviewed seven rodent models: olfactory bulbectomy, chronic mild stress, chronic forced swim test, novelty-induced hypophagia (NIH), novelty-suppressed feeding (NSF), social defeat stress, and learned helplessness.
• Examined effects of classical antidepressants and fast-acting clinical treatments (electroconvulsive shock therapy, sleep deprivation, ketamine, scopolamine, GLYX-13, pindolol).
• Discussed compounds with preclinical fast-onset antidepressant-like effects.

Main Results:

• Several rodent models are used to assess antidepressant onset, but few are thoroughly tested for predictive validity.
• Classical antidepressants show delayed effects, while treatments like ketamine and GLYX-13 demonstrate rapid antidepressant actions.
• Novel compounds targeting serotonin, NMDA, TREK-1, and mGluR receptors show promise for fast-onset antidepressant effects.

Conclusions:

• Rodent models are essential for preclinical identification of fast-onset antidepressants.
• Further validation of these models is needed to accurately predict therapeutic onset.
• Identifying and developing fast-acting antidepressants can significantly reduce the burden of depression and suicide risk.