The effects of colchicine and vinblastine on memory in chicks

Colchicine, injected bilaterally into the forebrain of day-old chicks at times before and after one-trial avoidance learning, produced transient amnesia for one to three hours after learning, that could not be accounted for as a perceptual or attentional defect. The amnesia was dose dependent and was produced only when injections occurred within a limited period before and after learning. No amnesia occurred when injections were given 120 min before or 60 min later than the learning trial, nor at times prior to the retrieval test. During the amnesic period, new learning could occur and be retrieved 15 min later. The amnesia could be overcome by retention-testing or by a new, related, learning experience before or up to 30 min after onset of amnesia. Control birds injected with saline or lumicolchicine, a biologically inactive derivative of colchicine, showed normal retention. Vinblastine sulphate, which also interrupts microtubular networks and hence axonal flow, had no amnesic properties. Colchicine injections had no effect on the levels of acetylcholinesterase, choline acetyltransferase, glutamic acid decarboxylase, and muscarinic acetylcholine receptors in the whole forebrain or in forebrain synaptosomes during the amnesic period. Nor did colchicine injections affect amino acid uptake and protein or glycoprotein synthesis before or during the amnesic period, although there was 10-20% inhibition of protein synthesis 5 h after injection. Thus over the amnesic period, there was no evidence of gross perturbation of brain function. Electron microscopy showed microtubules intact within 1 mm of the injection site 2.5 after injection. Oedema was found at this time in chicks injected with a high dose (100 micrograms) shown to disturb behaviour grossly, but not with a low dose (5 micrograms) which caused amnesia. Transient amnesia for one-trial avoidance learning is most probably caused by secondary effects of colchicine on nerve cell function. We suggest that the amnesic episode represents destruction of one of the stages of a multiple independent parallel process of memory consolidation.