Acute intracerebroventricular injections of the mast cell degranulator compound [formula omitted] and behavior in rats

Abstract

The intracerebroventricular (ICV) injection of the mast cell degranulator Compound 48 80 (2.5–20.0 μg/kg) produced a marked behavioral syndrome in normotensive rats. The behaviors included head and body shakes, paw tremor, excessive grooming, unusual posture and gait, mild diarrhoea, piloerection, extreme agitation and irritability to touch, and a later phase of sedation. The highest doses (15 and 20 μg/kg) also produced catalepsy and episodes of “barrel rolling” (continous rolling of 1–8 turns around the longitudinal axis). These behaviors were observed for approximately 15–30 min although the sedation and catalepsy were maintained for 90–120 min. A second ICV injection of the 10 μg/kg dose of Compound 48 80 given 2 hr after an initial injection of this dose, produced a much reduced response and the numbers of head and body shakes, and episodes of paw tremor and grooming were between 20–30% of those produced by the first injection. The reduced effect of the second injection indicates that the behavioral effects of Compound 48 80 may arise from the acute degranulation of mast cells rather than direct effects on neuronal populations or the cerebral vasculature.