Prolonged effects of intracerebroventricular angiotensin II on drinking, eating and locomotor behavior in mice

The effects of centrally administered Angiotensin II (Ang II) on water and food intake in rodent models are well known. However, most studies have focused on the acute effects of intracranial Ang II. In the current study, we evaluated the effects of intracerebroventricular Ang II on food and water intake as well as locomotor activity over the entire dark phase of the murine diurnal cycle. Consistent with the previous reports, centrally administered Ang II rapidly stimulated water intake over the initial 1-hour period following treatment. However, this acute increase was immediately followed by a marked reduction in water intake resulting in decreased cumulative water intake approximately 7h after Ang II treatment. Pretreating animals with an Ang II type 1 receptor blocker, Losartan, completely antagonized the acute effect of Ang II and abolished initial water intake. In contrast, application of an Ang II type 2 receptor blocker, PD123319, abrogated the prolonged inhibitory effect of Ang II on drinking behavior and partially suppressed the initial increases in water intake. The suppressive effects of Ang II on cumulative food intake and spontaneous physical activity were also evident throughout the entire dark phase of diurnal cycle. These experiments are the first to suggest that the stimulatory effect of central Ang II treatment on water consumption is very temporary and that it causes a sustained suppressive effect on voluntary locomotion and food intake behavior in mice. ► Intracranial Ang II in mice causes an acute dipsogenic effect via the AT1 receptor. ► The effect is followed by sustained profound antidipsogenic effect. ► Central Ang II also suppresses voluntary locomotion and food consumption. ► Such inhibitory effects persist throughout the entire dark phase of diurnal cycle. ► The effects imply a role for central Ang II in regulating metabolic homeostasis.