title: Central histaminergic transmission modulates the ethanol induced anxiolysis in mice.
abstract: Intrigued by the report demonstrating an increase in brain histamine levels by ethanol administration and central histamine transmission to affect the anxiety related behaviors, the present study examined the permissive role of central histaminergic transmission in the acute anxiolytic-like effect of the ethanol on elevated plus maze (EPM) in mice. Results demonstrated that prior administration of the agents that are known to enhance the brain histamine transmission, i.e. low dose of histamine (0.1μg/mouse, i.c.v.) or histamine precursor, l-histidine (500, 1000mg/kg, i.p.) or low dose of histamine releasing agent (H3 receptor inverse agonist), thioperamide (2μg/mouse) attenuated the acute anitanxiety-like effect of ethanol (2g/kg, i.p, 8% w/v) in mice on EPM. However, pre-treatment with the H1 receptor antagonist, cetirizine (0.1μg/mouse, i.c.v.) or H2 receptor antagonist, ranitidine (50μg/mouse, i.c.v.) failed to affect the attenuating effect of low dose of histamine on ethanol induced anxiolysis. On the other hand, only H1 receptor antagonist, cetirizine (0.1μg/mouse, i.c.v.) was able to partially reverse the attenuation of ethanol induced anxiolysis by l-histidine (1000mg/kg, i.p.). Surprisingly, in mice pre-treated with the higher dose of histamine (50μg/mouse, i.c.v.) or thioperamide (10μg/mouse, i.c.v.), the ethanol (2g/kg, i.p.) induced antianxiety-like effect was further enhanced on EPM. Furthermore, this potentiating effect of high dose of histamine on the ethanol (2g/kg, i.p.) was exacerbated on pre-treatment with the H1 receptor antagonist, cetirizine, while H2 receptor antagonist, ranitidine completely reversed this action of high dose of histamine on ethanol. Supportive to these results, i.c.v. pre-treatment with H1 receptor agonist, FMPH (2, 6.5μg/mouse, i.c.v.) attenuated while H2 receptor agonist, amthamine (0.1, 0.5μg/mouse, i.c.v.) enhanced the ethanol induced anxiolysis in mice. Thus, it is reasonable to contemplate that central histaminergic transmission functions to negatively modulate the acute ethanol-induced anxiolysis probably via stimulation of postsynaptic H1 receptor and histamine might contribute to the anxiolytic action of ethanol via H2 receptor activation.
authors.affiliation: Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas University (A Central University), Koni, Bilaspur, Chhattisgarh, India.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Verma
authors.affiliation: Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas University (A Central University), Koni, Bilaspur, Chhattisgarh, India. Electronic address: nishant.s.jain@hotmail.com.
authors.forename: Nishant S
authors.initials: NS
authors.lastname: Jain
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects; D017332:Cetirizine / Q000008:administration & dosage; D000431:Ethanol / Q000008:administration & dosage*; D006632:Histamine / Q000008:administration & dosage / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000008:administration & dosage; D054828:Histamine H3 Antagonists; D006639:Histidine / Q000008:administration & dosage; D008297:Male; D051379:Mice; D010880:Piperidines / Q000008:administration & dosage; D011969:Receptors, Histamine H1 / Q000502:physiology*; D018100:Receptors, Histamine H3 / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D014151:Anti-Anxiety Agents; D006634:Histamine H1 Antagonists; D054828:Histamine H3 Antagonists; D010880:Piperidines; D011969:Receptors, Histamine H1; D018100:Receptors, Histamine H3; D000431:Ethanol; D006639:Histidine; D006632:Histamine; C052075:thioperamide; D017332:Cetirizine
keywords: Anxiety; EPM; Ethanol; Histamine; Histamine receptors; l-Histidine