Possible contributory role of the central histaminergic system in the forced swimming model.
Forced swimming is considered to bring about a depressive or despair state in experimental animals, usually manifested as immobility. Levoprotiline (CAS 76496-68-9), a new antidepressant, clearly reduced the duration of immobility in the forced swimming model in mice. As levoprotiline does not inhibit noradrenaline or serotonin reuptake, this effect did not seem to have been brought about through central monoaminergic systems. Histamine and tele-methylhistamine levels, the main metabolite of histamine in the cerebral cortex, were found to be significantly increased in the forced swimming model. Since the only significant known effect of levoprotiline on the neurotransmitter system is its histamine H1 receptor antagonism, a possible contribution of the central histaminergic system to the forced swimming model is proposed. The action of mepyramine, a histamine H1 receptor antagonist in reducing the duration of immobility seemed to support this proposition. It should be noted that antihistaminergic properties are shared by many antidepressant drugs.
Noguchi
S
S
Pre-Clinical Research Department, Ciba-Geigy Limited, Takarazuka, Japan.
Fukuda
Y
Y
Inukai
T
T
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D002490:Central Nervous System / Q000502:physiology*; D003866:Depressive Disorder / Q000503:physiopathology*; D004195:Disease Models, Animal; D006632:Histamine / Q000502:physiology*; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives / Q000494:pharmacology; D008761:Methylhistamines / Q000378:metabolism; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011738:Pyrilamine / Q000494:pharmacology; D013550:Swimming
D000928:Antidepressive Agents; D008761:Methylhistamines; D008376:Maprotiline; C027299:hydroxymaprotilin; D006632:Histamine; D011738:Pyrilamine; C020404:tele-methylhistamine