Does anxiety underly imidazole-induced behavioural effects in the rat?

Abstract

Since behavioural symptoms (tremor, irritability, pilo-erection and shaking) induced by imidazole (IMID) in rats suggested an underlying modification of arousal and/or emotionality, further studies were performed in order to extend the range of behavioural influences of IMID. In the open-field test, IMID (37.5–300 mg/kg IP) inhibited crossing and rearing in a dose-dependent fashion, this effect being long lasting (about 3 h at 75 mg/kg). Yohimbine (YOH) (1, 5 and 10 mg/kg IP), described as anxiogenic and fear-inducing in animals and in man, when investigated in this same test, inhibited the activity of rats similarly to IMID. Since diazepam (0.5 and 1 mg/kg) but not clonidine (0.075 and 0.150 mg/kg IP) pretreatment reversed IMID- and YOH-induced hypomotility, the hypothesis that IMID effects in the open field might reflect an anxiety-like state was investigated by means of social interaction and x-maze, two tests considered highly specific for anxiety studies. The data obtained show that IMID depresses social interactions only at doses inhibiting motor activity; YOH, in our experimental conditions, produced a similar effect. In an elevated x-maze, with alternate open and closed arms, IMID (37.5 and 75 mg/kg) decreased the proportion of open-arm entries and the time spent in them, an effect prevented by diazepam pretreatment (1 mg/kg IP). Finally, mean arterial pressure (MAP) was assessed in anesthetized rats treated with IMID and YOH at doses equivalent as regards behavioural effects. MAP was increased by IMID whether IP or IV and decreased by YOH; moreover, YOH, as expected, antagonized clonidine-induced hypotension, while IMID was ineffective. In conclusion, regardless of the possible receptors underlying the results obtained, IMID emerges as a drug able to exert potent effects on emotional reactivity and blood pressure of rats very similar to YOH in behavioural but not in cardiovascular experiments.