Activity change as the cause of apparent aversiveness during prolonged hypothalamic stimulation.

minutes before training (5), we sought to determine whether such injections of amphetamine also antagonize the effects of cycloheximide on activity. Mice were first injected with cycloheximide; 3 hours and 45 minutes later, they were injected subcutaneously with amphetamine (1 mg/kg) or saline. This interval between drug injections is the same one employed in memory studies, where amphetamine, but not saline, was found to antagonize the effect of cycloheximide. Activity was measured continuously during the 1st hour after amphetamine or saline injection. Mice given cycloheximide and saline (N = 8) exhibited marked inhibition of activity during this period; their activity was significantly less than that of mice given only saline (Fig. 1) before activity (P < .01). Amphetamine (N= 8) did not antagonize the depression of activity. Thus, the effect of amphetamine on memory in cycloheximide-treated mice (5) is not correlated with a measurable increase in activity. We conclude from these studies (i) that cycloheximide affects activity by acting on the brain, (ii) that this action is unrelated to its inhibition of protein synthesis, land (iii) that these effects of cycloheximide on activity do not appear to be responsible for its amnesic action. It is possible, of course, that cycloheximide has some other property, unrelated to inhibition of cerebral protein synthesis, that is responsible for its amnesic effect. DAVID S. SEGAL LARRY R. SQUIRE SAMUEL H. BARONDES Department of Psychiatry, University of California, San Diego, La Jolla 92037