HISTAMINE-RELEASE FROM THE HYPOTHALAMUS INDUCED BY GRAVITY CHANGE IN RATS AND SPACE MOTION SICKNESS

Freely moving rats were exposed to 2 g hypergravity in an animal centr ifuge device to produce motion sickness. Histamine release from the an terior hypothalamus of the rats was measured in vivo with a microdialy sis technique. After a 2-h load of 2 g hypergravity, rats ate kaolin. Because pica, eating a nonnutritive substance such as kaolin, is a beh avioral index of motion sickness in rats, this finding indicates that the rats suffered from motion sickness. During 2 g hypergravity for 2- h, histamine release from the hypothalamus was transiently increased. In contrast, neither the transient increase of histamine release nor t he kaolin consumption were induced by 2 g hypergravity in bilaterally labyrinthectomized rats. Pretreatment with alpha-fluoromethylhistidine , an inhibitor of histamine-synthesizing enzyme, decreased both the ba sal and hypergravity-induced releases of histamine from the hypothalam us and suppressed the kaolin consumption induced by hypergravity. Take n together, these findings suggest that the vestibular information of changes in gravity activate the histaminergic neuron system, resulting in the development of motion sickness. More prolonged stimulation, a 4-h load of 2 g hypergravity, induced significant increase of kaolin c onsumption on postdays 1-3, though rats ate kaolin on postdays 1-2 aft er 2 g hypergravity for 2 h. During 2 g hypergravity for 4 h, the init ial transient increase of histamine release was followed by the gradua l increase of histamine release after the end of centrifugation. It is suggested that rats adapted to the hypergravity environment after cen trifugation for 4 h, but not 2 h, so that the change in gravity from 2 g to 1 g became a provocative stimulation. We, therefore, concluded t hat motion sickness in rats induced by a negative change in gravity ca n be used as a simulation of space motion sickness, which is induced b y exposure to microgravity. Histaminergic activation in the developmen t of motion sickness induced by negative change in gravity might be an underlying mechanism of space motion sickness. (C) 1997 Elsevier Scie nce Inc.