HISTAMINERGIC H-2 ACTION PROTECTS HIPPOCAMPAL CA1 NEURONS BY PROLONGING THE ONSET OF THE ANOXIC DEPOLARIZATION IN GERBILS

The central histaminergic action on ischemia-induced neuronal damage w as examined by evaluating the histological outcome and the direct curr ent (DC) potential shift in the hippocampal CA1 region in gerbils. An intracerebroventricular administration of histamine (10-100 nmol) impr oved the delayed ischemic damage in hippocampal CA1 pyramidal cells pr oduced by 3 min of transient forebrain ischemia. A high dose (75 nmol) of mepyramine, an H-1 antagonist, aggravated ischemia-induced neurona l damage, but not a low dose (0.75 nmol). Administration of cimetidine (4 nmol) and ranitidine (3 nmol), H-2 antagonists, aggravated the neu ronal damage. An injection of histamine (100 nmol) prolonged the onset time of the ischemia-induced sudden shift in the extracellular DC pot ential (anoxic depolarization; AD) to 133% of that in control animals. Administration of mepyramine (75 nmol) did not markedly change the AD , whereas injections of cimetidine (40 nmol) and ranitidine (3 nmol) r educed the onset latency to 47 and 45%, respectively. These findings s uggest that the central H-2 action serves to protect neurons by delayi ng the onset of AD in gerbils.