Role of hippocampal nitrergic neurotransmission in behavioral and cardiovascular dysfunctions evoked by chronic social stress

Abstract

Increased nitric oxide (NO) levels have been identified in the hippocampus of animals subjected to social isolation. However, a role of this change in behavioral and physiological changes evoked by isolation has never been evaluated. Thus, this study investigated the involvement of nitrergic neurotransmission acting via the neuronal isoform of nitric oxide synthase (nNOS) within the dorsal hippocampus in behavioral and cardiovascular changes in isolated reared rats. For this, male rats were isolated from weaning at 21 days postnatal for 40 days. We identified that social isolation increased hippocampal NO formation and nNOS expression. Besides, anxiogenic- and depressive-like effect identified in isolated animals were not affected by intra-hippocampal microinjection of either the NO scavenger carboxy-PTIO or the selective nNOS inhibitor Nω-Propyl-L-arginine (NPLA). Isolation also increased basal arterial pressure, impaired the baroreflex function and decreased the tachycardia to restraint stress. The effects in restraint-evoked tachycardia were inhibited by hippocampal treatment with either carboxy-PTIO or NPLA. Intra-hippocampal administration of either carboxy-PTIO or NPLA also enhanced the pressor response to restraint in isolated, but not in control animals. Taken together, these findings indicate that increased NO release within the dorsal hippocampus is involved in impairment of cardiovascular responses to a novel stressor, but not in behavioral effects and baroreflex changes, evoked by social isolation. Furthermore, exposure to this stressor evokes the emergence of an inhibitory role of hippocampal nNOS activation in cardiovascular changes to a novel stressor, which might constitute a prominent adaptive response.