Recent preclinical studies have demonstrated that the administration of the highly selective 5-HT1A receptor biased agonist, NLX-101 (also known as F15599), results in a rapid antidepressant-like response, both in naïve animals [12,13] and rodent models of depression [14,15], presumably through the activation of cortical 5-HT1A receptors. This evidence concerns the gene HTR1A and major depressive disorder.