Effects of anisomycin on brain protein synthesis and passive avoidance learning in newborn chicks.

The effects of anisomycin (ANM) on newborn chicks have been studied with respect to brain protein synthesis, growth, EEG, toxicity, and several passive avoidance learning tasks. It was found that intracerebral ANM (80 nmol) gave a maximum inhibition of brain protein synthesis of 30%, while a combination of subcutaneous (10 mumol; 53 mg/kg) plus intracerebral (80 nmol; 21 mug) ANM inhibited by 91% in the first 2 hr and by 75% in the subsequent 2 hr period. Cycloheximide (CXM) also in combined injections at the same doses as ANM, inhibited by 97% in the 4 hr that followed injection. However, all the CXM-injected chicks were dead by 18 hr, while the lethality of ANM did not differ from that of saline. ANM also did not affect EEG measured at 1, 3, 5, or 24 hr following the subcutaneous plus intracerebral injections, nor did ANM affect body or brain growth curves or brain protein accretion. In the learning experiments, animals were initially trained to peck at water-coated metal spheres (type A learning) or at water imbibed birdseed (types B and C learning) in less than 1 sec, and were exposed to the same lures treated with the aversant methylanthranilate (MeA) one day later on one occasion (types A and B learning) or exposed twice (type C learning) and tested for learning retention one day later. Learning criterion was set as failure to peck at the lure during the first 20 sec of presentation. If ANM was injected 1 hr prior to MeA exposure, large and highly significant memory deficits were found during the retention test, as compared with saline injected controls. No effect of ANM was seen, however, if it was injected one day after learning, indicating that it did not interfere with retrieval mechanisms. ANM also decreased the external manifestations of fear or displeasure that chicks express during retention testing. Such manifestations have a high correlation with pecking suppression (r = 0.88, P less than 0.001).