Preclinical modeling of primal emotional affects (SEEKING, PANIC and PLAY): Gateways to the development of new treatments for depression

Mammalian brains contain at least 7 primal emotional systems - SEEKING, RAGE, FEAR, LUST, CARE, PANIC and PLAY (capitalization reflects a proposed primary-process terminology, to minimize semantic confusions and mereological fallacies). These systems help organisms feel affectively balanced (e.g. euthymic) and unbalanced (e.g. depressive, irritable, manic), providing novel insights for understanding human psychopathologies. Three systems are especially important for understanding depression: The separation distress (PANIC) system mediates the psychic pain of separation distress (i.e. excessive sadness and grief), which can be counteracted by minimizing PANIC arousals (as with low-dose opioids). Depressive dysphoria also arises from reduced brain reward-seeking and related play urges (namely diminished enthusiasm (SEEKING) and joyful exuberance (PLAY) which promote sustained amotivational states). We describe how an understanding of these fundamental emotional circuits can promote the development of novel antidepressive therapeutics - (i) low-dose buprenorphine to counteract depression and suicidal ideation emanating from too much psychic pain (PANIC overarousal), (ii) direct stimulation of the SEEKING system to counteract amotivational dysphoria, and (iii) the discovery and initial clinical testing of social-joy-promoting molecules derived from the analysis of the PLAY system.