Affective neuroscience strategies for understanding and treating depression: From preclinical models to three novel therapeutics

Mammalian brains contain seven primary-process affective substrates for primal emotional feelings and behaviors. Scientific labels for these interactive systems are SEEKING, RAGE, FEAR, LUST, CARE, PANIC, and PLAY. Understanding these brain substrates could lead to new treatments of emotional disturbances that accompany mental illnesses. We summarize how understanding of such emotional affects—especially those of separation distress (PANIC, promoting excessive sadness and grief), SEEKING (promoting enthusiasm), and PLAY (promoting social joy)—may regulate depressive affect through a focus on the following: (a) reducing PANIC, namely, “psychic pain” with “safe opioids” such as buprenorphine; (b) facilitating enthusiasm with deep brain stimulation of the transdiencephalic medial forebrain bundle–based SEEKING urges; and (c) how studies of brain neurochemical pathways that facilitate social joy (PLAY) in animals have yielded novel neurochemical interventions (e.g., GLYX-13, a partial agonist of glycine receptors) currently in successful human testing. Affective neuroscience principles that have led to these advances are summarized.