Nature and amplitude of the effects of acetoxycycloheximide on the retention of an instrumental task in mice (author's transl)

Mice injected subcutaneously with AXM (7 mg/kg) 60 minutes or less after acquisition of a nondiscriminative instrumental task, show low levels of lever press responding, when tested 6 days after the treatment. AXM injected 180 min after acquisition has no effect whatsoever on the performance. The analysis of various parameters such as, (1) the number of nonreinforced responses (A) preceding the first reinforced response (AR), and (2) the latency of the first reinforced response, shows that only the animals treated with AXM during the first 3 min following acquisition differ significantly from the control animals: they seem to have forgotten the significance of the lever. On the contrary, the low levels of responding observed in the animals treated 30–60 min after acquisition does not seem to be due to a nonretention of the significance of the liver. The mechanisms by which the AXM affects the level of responding remain obscure.     

Effects of acetoxycycloheximide and anisomycin on approach and escape responses to hypothalamic stimulation

The effects of acetoxycycloheximide (AXM) (7 mg/kg) and anisomycin (ANI) (25 and 150 mg/kg) on approach and escape responses induced by hypothalamic stimulation were studied in a situation in which male Swiss mice could initiate a continuous brain stimulation train by pressing a lever at one end of a box (ON-lever) and terminate this stimulation train by pressing a lever at the other end of the box (OFF-lever). AXM and ANI induced a large decrease in ON-OFF responses regardless of the level of stimulation presented (a low level just above the stimulation threshold and a high level which was twice the low level). Correspondingly, a significant increase was observed in the mean time during which animals remained unstimulated (NST) whereas mean time during which animals remained stimulated (ST) increased only slightly. The relative NST increase after treatment was always greater than the relative ST increase either at sites where before treatment NST was greater than ST or at sites where NST was shorter than ST. However, the animals in this latter electrode placement group (ST greater than NST) continued to shuttle and to make lever-pressing responses on the ON-lever, whereas the animals in the other placement group (ST less than NST) did not. These results are discussed in terms of possible interactions between disruptions of reinforcing systems induced by protein inhibitors and their effects on memory.     

Modifications of bioelectrical activity of the hippocampus of mice induced by acetoxycycloheximide (author's transl)

Swiss male mice were chronically implanted with electrodes in dorsal hippocampus and in mesencephalon (mesencephalic reticular formation and central gray). Effects of acetoxycycloheximide (AXM) on spontaneous bioelectrical activity of the hippocampus and on hippocampal response to mesencephalic stimulation were analyzed. AXM injection (7 mg/kg) provoked a decrease in both frequency and amplitude of the spontaneous hippcampal activity and, in particular, a marked decrease in the theta activity in the 6–10 cps band. AXM induced no change in the mesencephalic stimulation threshold shown to induce hippocampal theta rhythm. A decrease in both frequency and amplitude of the theta rhythm induced by mesencephalic stimulation was, however, recorded. These alterations, which appeared during the first hour following AXM injection, were especially obvious from 3 to 6 hours after treatment. From 7 to 24 hours after injection, the hippocampal bioelectrical activity, either spontaneous or induced, recovered gradually its initial characteristics.     

Effects of protein synthesis inhibition on memory for active avoidance training.

Inhibition of brain protein synthesis by anisomycin and acetoxycycloheximide was studied in mice for its biochemical and behavioral effects. By employing both drugs in low doses in a series of injections, we were able to maintain inhibition of protein synthesis of 80% or greater for up to 14 hr without causing detectable permanent physiological impairment. The drugs were employed as amnestic agents in mice trained to avoid footshock in a T-maze. As the duration of inhibition increased, the percentage of mice classed as amnesic increased. This amnesia could be reduced by increasing (a) the rate of acquisition, or (b) the number of training trials. Anisomycin was shown to cause a significant degree of amnesia for the escape component as well as the avoidance component of the learning. A single injection of anisomycin given 15 min prior to training did not cause significant changes in the acquisition or retention of avoidance conditioning, when comparison was made with saline-injected controls. Only additional injections given after training to prolong inhibition caused amnesia. Thus, those injections critical in obtaining amnesia were given at a time at which interference with acquisition could not have occurred, so the results bear clearly on memory processes.     

Aversive effects and retention impairment induced by acetoxycycloheximide in an instrumental task.

AXM, when subcutaneously injected during the first 3 min following the acquisition of a nondiscriminative instrumental learning task, induced an aversion for the food reinforcement which had been associated with the training situation and with the pharmacological treatment. The high number of nonreinforced responses preceding the first reinforced response(RR) that animals performed when tested 6 days after AXM treatment, was not due to forgetting of the lever significance, but to this aversion. Animals treated with AXM showed low levels of lever pressing response and long latencies for their first RR; this deficit did not seem only to be due to food reinforcement aversion; it disappeared, as well as food aversion, when food reinforcement which had been associated with the learning situation and to treatment, was added to the daily feeding regimen during treatment-test interval. It has been shown, moreover, that more than 90 percent of cerebral protein synthesis was inhibited during the 5 hr following subcutaneous AXM injection. These findings are interpreted as an indication that AXM does not affect memory consolidation of a non discriminative instrumental learning.     

The effect of puromycin on neuromuscular transmission

Twitch tensions of directly and indirectly stimulated frog sartorius muscles and the mechanical responses to exogenous acetylcholine were recorded in the presence and absence of puromycin. This drug reduced the response to acetylcholine and indirect stimulation but did not affect the response of directly stimulated frog sartorius muscles. These effects were reversible. Summed motor end plate of frog sartorius muscles were recorded in the absence and presence of puromycin and acetoxycycloheximide. Puromycin reduced the magnitude of the motor end plate potential but acetoxycycloheximide did not. This effect of puromycin was only partially reversible. The effects of curare on twitch tension of indirectly stimulated muscles and on the motor end plate potential were the effects of puromycin.