EFFECTS OF HISTAMINE, H1-RECEPTOR AND H2-RECEPTOR ANTAGONISTS ON THE ACTIVITY OF SEROTONERGIC NEURONS IN THE DORSAL RAPHE NUCLEUS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 227  (2) , 517-523
Abstract
The effects of histamine applied by microiontophoresis onto serotonin-containing (serotonergic) cells recorded extracellularly in the dorsal raphe nucleus of the rat were studied. Application of histamine at low iontophoretic currents (1-5 nA) produced a rapid depression of the firing of all serotonergic neurons tested. The H1-receptor antagonists mepyramine and diphenhydramine were unable to attenuate the histamine-induced response. Antagonism of the effect of histamine by the ionotophoretic application of the H2-receptor antagonists cimetidine and metiamide was not possible to evaluate since both exerted potent inhibitory effects by themselves. The nonimidazole-derived H2-receptor antagonist ranitidine, which had no effect by itself, selectively antagonized the histamine-induced depression of neuronal activity. Histidine, 3-methylhistamine and a variety of histamine agonists selective for H1- or H2-receptors were unable to mimic the effect of histamine in dorsal raphe. Histamine''s effects may, in part, be mediated at a GABA receptor complex as the GABA antagonists bicuculline and picrotoxin rapidly and reversibly antagonized both the histamine- and the cimetidine-induced depression of serotonin cell firing; the glycine antagonist strychnine selectively blocked the inhibitory effect of glycine without altering the histamine-induced response. These data show an inhibitory effect of histamine on serotonin-containing neurons in the dorsal raphe; this effect may be partially mediated at a subtype of H2-receptor. The inhibitory effects of histamine and cimetidine observed in the dorsal raphe nucleus may result, in part, from an action directly or indirectly at a GABA receptor complex.