Neuropeptidergic Control of an Internal Brain State Produced by Prolonged Social Isolation Stress

Prolonged periods of social isolation can generate an internal state that exerts profound effects on the brain and behavior. However, the neurobiological underpinnings of protracted social isolation have been relatively understudied. Here, we review recent literature implicating peptide neuromodulators in the establishment and maintenance of such internal states. More specifically, we describe an evolutionarily conserved role for the neuropeptide tachykinin in the control of social isolation–induced aggression and review recent data that elucidate the manner by which Tac2 controls the widespread effects of social isolation on behavior in mice. Last, we discuss potential roles for additional neuromodulators in controlling social isolation and a more general role for Tac2 in the response to other forms of stress.