Evidence for excitatory actions of histamine on supraoptic neurons in vitro: mediation by an H1-type receptor.

The effects of histamine on the firing of supraoptic neurosecretory neurons in the rat were examined in vitro using acutely prepared, hypothalamo-neurohypophysial explants perifused with an artificial cerebrospinal fluid. Extracellular action potentials meeting the criteria of antidromic invasion from neurohypophysial stalk stimulation were recorded from 135 neurons in the tuberal portion of the supraoptic nucleus, which lies superficially along the tuber cinereum and consists of mostly vasopressin-containing neurons. Units could be classified as slow/silent (76.3%), phasic (21.5%) or continuous (2.2%) on the basis of their spontaneous activity. Histamine applied briefly to the perifusate excited approximately one-third of the slow silent neurons and approximately two-thirds of the phasic neurons, with a wide range (10(-3)-10(-9)) in the effective concentration across neurons. The H1-receptor agonists 2-pyridylethylamine and 2-thiazolylethylamine mimicked these excitations in 10 of 12 and 3 of 6 neurons tested, respectively. The H2-receptor agonists dimaprit (4 neurons) and impromidine (5 neurons) failed to excite any of the tested neurons previously excited by histamine. The H1-receptor antagonist promethazine antagonized histamine's excitatory effect in 8 of 9 cells, while the H2-receptor antagonist cimetidine had little effect on the 9 cells tested. Histamine also modified bursts of activity induced in some slow/silent neurons by antidromic stimulation without having an observable effect in the absence of an antidromic burst. In 10 of 18 neurons histamine produced an elongation of burst duration and a modest increase in intraburst firing rate when applied during an antidromically evoked burst. In an additional 5 of 17 neurons, which had neither previously responded to histamine nor shown an antidromically-evoked burst, the pairing of histamine application and antidromic shocks resulted in an antidromically evoked burst. The effects of histamine on evoked bursts also appeared to be mediated by an H1-receptor. Histamine's excitation of supraoptic neurons is thus dependent on the electrical activity expressed by the neuron at the time of testing. Conductances activated by depolarization of the neuron may be modified by histamine or this compound may alter the threshold for burst generation. Considered with data showing H1-receptor localization and histamine-immunoreactive fibers within the supraoptic nucleus, the present results, as well as those showing the potency of centrally applied histamine in releasing vasopressin, suggest histamine may act physiologically by altering the electrical activity of vasopressin-secreting neurons.