Lateralized effects of medial prefrontal cortex lesions on neuroendocrine and autonomic stress responses in rats

The medial prefrontal cortex (mPFC) is highly activated by stress and modul ates neuroendocrine and autonomic function. Dopaminergic inputs to mPFC fac ilitate coping ability and demonstrate considerable hemispheric functional lateralization. The present study investigated the potentially lateralized regulation of stress responses at the level of mPFC output neurons, using i botenic acid lesions. Neuroendocrine function was assessed by plasma cortic osterone increases in response to acute or repeated 20 min restraint stress . The primary index of autonomic activation was gastric ulcer development d uring a separate cold restraint stress. Restraint-induced defecation was al so monitored. Plasma corticosterone levels were markedly lower in response to repeated versus acute restraint stress. In acutely restrained animals, r ight or bilateral, but not left mPFC lesions, decreased prestress corticost erone levels, whereas in repeatedly restrained rats, the same lesions signi ficantly reduced the peak stress-induced corticosterone response. Stress ul cer development (after a single cold restraint stress) was greatly reduced by either right or bilateral mPFC lesions but was unaffected by left lesion s. Restraint-induced defecation was elevated in animals with left mPFC lesi ons. Finally, a left biased asymmetry in adrenal gland weights was observed across animals, which was unaffected by mPFC lesions. The results suggest that mPFC output neurons demonstrate an intrinsic right brain specializatio n in both neuroendocrine and autonomic activation. Such findings may be par ticularly relevant to clinical depression which is associated with both dis turbances in stress regulatory systems and hemispheric imbalances in prefro ntal function.