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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 sys- tems – SEEKING, RAGE, FEAR, LUST, CARE, PANIC and PLAY (capitalization reflects a proposed primary-process terminol- ogy, to minimize semantic confusions and mereological falla- cies). 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 (PAN- IC) 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). De- pressive dysphoria also arises from reduced brain reward- seeking and related play urges (namely diminished enthusi- asm (SEEKING) and joyful exuberance (PLAY) which promote sustained amotivational states). We describe how an under- standing of these fundamental emotional circuits can pro- mote 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 sys- tem to counteract amotivational dysphoria, and (iii) the dis- covery and initial clinical testing of social-joy-promoting mol- ecules derived from the analysis of the PLAY system.