Antidepressant properties of the triazolobenzodiazepines alprazolam and adinazolam: studies on the olfactory bulbectomized rat model of depression.

Chronically administered alprazolam and adinazolam attenuated the hyperactivity of bilaterally bulbectomized rats when placed in a stressful, novel environment (‘open field’ apparatus). These drugs had no effect on the activities of sham operated animals under the same experimental conditions. In other studies in these laboratories, clinically effective antidepressant drugs have been shown to have a qualitatively similar effect to alprazolam and adinazolam. Chronically administered diazepam and phenobarbitone did not affect the hyperactivity of bulbectomized rats in the ‘open field’ apparatus. No difference could be found between the behaviour of bulbectomized rats and the sham operated controls when the animals were placed in a novel, non‐stressful environment (‘hole board’ apparatus and Y‐maze). Chronic treatment of either the lesioned or non‐lesioned animals with alprazolam or adinazolam did not cause any change in the behaviour of the animals in these situations. This suggests that the behaviour of the rat on the ‘hole board’ is not a reliable indication of anti‐ anxiety activity for chronically administered benzodiazepines. When unstarved lesioned and non‐lesioned animals were given a choice of five palatable foods for a period of 1 h, slight differences in preference for the type of food chosen could be detected. Thus unsweetened biscuit (‘cream crackers’) was the most preferred choice of the sham operated rats while cheese and chocolate were the least preferred. Bulbectomized rats showed a more varied food choice, with processed meat (‘corned beef’) and raisins being preferred to biscuit in two out of four groups. Chronic treatment with either alprazolam or adinazolam did not appear to affect the food preference.(ABSTRACT TRUNCATED AT 250 WORDS)