Biochemical effects of cycloheximide in developing chick brain

The timecourses of inhibition of protein synthesis in forebrain roof 15 min to 24 hr after either intracerebral or peripheral injection of 40 microgram of cycloheximide (CXM), show maximum inhibition (68--85%) 1 hr after injection in 12 hr, 2-day- and 16-day-old chicks. In 2-day-old chicks, the level of free lysine was elevated by around 250% 1 hr after intracerebral injection of CXM. The total radioactivity in the forebrain roof/mg protein following peripheral injection of labelled lysine increased by around 80% compared to saline controls. Following unilateral injection of 20 microgram in 25 microliter CXM into a forebrain hemisphere, the inhibition of protein synthesis spread to the opposite forebrain hemisphere and both optic lobes within 5 min. Smaller volumes did not seem to give a clear unilateral inhibition capable of explaining the unilateral behavioural differences which have been reported. Central injection of CXM in 2- and 16-day-old chicks, resulted in an inhibition of liver protein synthesis of 55% and 40%, respectively. There were also gross signs of pathological effects in the liver and gall bladder. The implications of these effects of CXM are discussed in terms of the use of the drug in behavioural experiments.