Passive avoidance impairment in rats following cycloheximide injection into the amygdala

Cycloheximide (CHX:1, 10 or 20 microg) was injected via indwelling cannulas into various regions of the rat brain and its effects on passive avoidance training were studied. Rats with 10 or 20 microg of CHX injected into the amygdala immediately after the training footshock exhibited amnesia for the learning experience when tested after 24 h. In contrast, animals injected with 20 microg of CHX at a site either in the internal capsule only 2 mm above the amygdaloid injection site or in the frontal cortex showed no retention deficit when tested after 24 h. A quantitative examination of protein synthesis in brain halves 30 min after unilateral injection of 20 microg of CHX into the amygdala demonstrated that total protein synthesis was inhibited by less than 10%. Autoradiographic studies revealed that this inhibition resulted from a profound, highly localized inhibition of protein synthesis in areas immediately adjacent to the cannula. A comparison of the regional patterns of protein synthesis inhibition caused by injection of CHX into either the amygdala or internal capsule suggested that CHX might produce amnesia by virtue of its localized effect on the amygdala. Control experiments revealed that injection of 20 microg CHX into the amygdala had no effect on short-term retention, or short-term performance. Injection of 20 microg of CHX into the amygdala 12 h after the footshock had no effect on long-term retention. The observed impairment of retention was shown to be dose-dependent as injection of 1 microg of CHX into the amygdala was without effect. In addition, it was demonstrated that the CHX-induced amnesia did not result from induction of local seizure activity. These data show that localized injections of small amounts of CHX into the amygdala can produce deficient memory of a training experience even though total brain protein synthesis is only slightly inhibited.