Histaminergic modulation of stress-induced analgesia and cognitive dysfunction

Physiological stress is known to produce analgesia and memory disruption. A large body of evidence favors the nonopiate mediation of stress-induced analgesia. It is suggested that brain histamine mediates nonopiate analgesia and participates in learning and memory in rodents. Histamine is released during stress, although the nature of histaminergic involvement in stress response is not clearly defined. Therefore, we studied the effect of L-histidine and histamine-receptor antagonists on antinociception and impaired retention induced by immobilization stress. In the present study, immobilization stress produced a naloxone-resistant analgesia that was potentiated by L-histidine and antagonized by pretreatment with the histamine receptor antagonists chlorpheniramine and cimetidine. L-histidine attenuated the memory disruption induced by immobilization stress, which was significantly reversed by chlorpheniramine but not by cimetidine. Thus the involvement of the central histaminergic system, through histamine H1- and H2-receptors, may be speculated in analgesia and cognitive deficit induced by immobilization stress.