Causes of changes in brain noradrenaline systems and later effects on responses to social stressors in rhesus monkeys: the cascade hypothesis.

Disruption of social attachments in social primates produces a protest-despair response. In rhesus monkeys, the response is probably adaptive in the feral environment, although the despair stage resembles human depression in many respects. The severity of the response varies between individuals and is affected by deprivation of certain classes of social stimuli during development. Social deprivation is associated with differences in the concentrations of noradrenaline (NA) in cerebrospinal fluid and in responses to agents that affect catecholamine systems. Thus, early rearing conditions and pre-existing genetic or perinatal differences between monkeys can have long-term effects on the response to social separation, and NA system release and/or receptor mechanisms are involved. NA systems appear to mediate adaptation to the environment from the level of perception to reorganization of neural tissue. Adaptation to the social environment may involve a cascade of changes that begins with behavioural coping attempts and terminates in structural reorganization of regions of the cerebral cortex. Processes at each level occur within environmentally appropriate but neurobiologically constrained time-frames. The cerebral NA system may be an adaptive mechanism that can fail or be damaged. Behavioural changes caused by such damage or failure would be manifested by inappropriate responses to environmental contingencies and inability to change behaviour to adapt to the prevailing environment. These features of NA system disorder could be common to depression and several other forms of human psychopathology.