It is also possible that stress habituation is mediated by structural alterations along stress integrative circuits. For example, repeated brief restraint, a treatment that generally causes habituation, causes retraction of basal dendrites of prefrontal cortical neurons (Brown et al., 2005), which may impact down-stream regulation of HPA axis responses. More prolonged restraint-exposure paradigms (6 h/day, 21 days) produces dendritic retraction and spine loss in the PFC (Vyas et al., 2002; Cook and Wellman, 2004; Radley et al., 2006, 2008) as well as retraction in subfield CA3 of the hippocampus (Magarinos and McEwen, 1995), while causing increased dendritic complexity in the basolateral amygdala (Vyas et al., 2002). Chronic restraint also increases branching of GABAergic interneurons in the PFC (Gilabert-Juan et al., 2012), suggestive of enhanced inhibition. Structural alterations may affect the excitability of neurons, which can then alter the overall balance of limbic inputs to neurons controlling stress responsiveness.
