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Effects of histamine, H1- and H2-receptor antagonists on the activity of serotonergic neurons in the dorsal raphe nucleus.
J Pharmacol Exp Ther. 1983 Nov; 227(2):517-23.JP

Abstract

We investigated the effects of histamine applied by microiontophoresis onto serotonin-containing (serotonergic) cells recorded extracellularly in the dorsal raphe nucleus of the rat. 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 iontophoretic application of the H2-receptor antagonists cimetidine and metiamide was not possible to evaluate since both were found to exert potent inhibitory effects by themselves. In contrast, 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 gamma-aminobutyric acid receptor complex as the gamma-aminobutyric acid 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. These data further indicate that 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 gamma-aminobutyric acid receptor complex.

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

6138428

Citation

Lakoski, J M., and G K. Aghajanian. "Effects of Histamine, H1- and H2-receptor Antagonists On the Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus." The Journal of Pharmacology and Experimental Therapeutics, vol. 227, no. 2, 1983, pp. 517-23.
Lakoski JM, Aghajanian GK. Effects of histamine, H1- and H2-receptor antagonists on the activity of serotonergic neurons in the dorsal raphe nucleus. J Pharmacol Exp Ther. 1983;227(2):517-23.
Lakoski, J. M., & Aghajanian, G. K. (1983). Effects of histamine, H1- and H2-receptor antagonists on the activity of serotonergic neurons in the dorsal raphe nucleus. The Journal of Pharmacology and Experimental Therapeutics, 227(2), 517-23.
Lakoski JM, Aghajanian GK. Effects of Histamine, H1- and H2-receptor Antagonists On the Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus. J Pharmacol Exp Ther. 1983;227(2):517-23. PubMed PMID: 6138428.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of histamine, H1- and H2-receptor antagonists on the activity of serotonergic neurons in the dorsal raphe nucleus. AU - Lakoski,J M, AU - Aghajanian,G K, PY - 1983/11/1/pubmed PY - 1983/11/1/medline PY - 1983/11/1/entrez SP - 517 EP - 23 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 227 IS - 2 N2 - We investigated the effects of histamine applied by microiontophoresis onto serotonin-containing (serotonergic) cells recorded extracellularly in the dorsal raphe nucleus of the rat. 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 iontophoretic application of the H2-receptor antagonists cimetidine and metiamide was not possible to evaluate since both were found to exert potent inhibitory effects by themselves. In contrast, 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 gamma-aminobutyric acid receptor complex as the gamma-aminobutyric acid 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. These data further indicate that 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 gamma-aminobutyric acid receptor complex. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/6138428/Effects_of_histamine_H1__and_H2_receptor_antagonists_on_the_activity_of_serotonergic_neurons_in_the_dorsal_raphe_nucleus_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6138428 DB - PRIME DP - Unbound Medicine ER -