Subamnesic cycloheximide treatment delays consolidation in mice.

Abstract

In the first experiment, groups of C57 BL/6J mice were given passive avoidance training and then administered different doses of cycloheximide (CYC) immediately, 30 min, or 1 hr after training. Only the highest dose (150 mg/kg) administered immediately or 30 min after training impaired memory when the mice were tested 72 hr after training. In the second experiment, mice were given a nonamnesic administration of CYC (30 mg/kg) or saline immediately after training and another injection of CYC (15 mg/kg, 30 mg/kg, or 75 mg/kg) or saline 1 hr after training. Single injections of CYC and the combination of 30 mg/kg +15 mg/kg did not impair memory, but the combinations of 30 mg/kg + 30 mg/kg and 30 mg/kg + 75 mg/kg did impair memory. The third experiment demonstrated that brief carbon dioxide anesthetization initiated immediately after training impairs memory. In the fourth experiment, mice were given either saline or 30 mg/kg CYC immediately after training and then subjected to either air or CO2 anesthetization 30 min after training. Only the group given 30 mg/kg CYC + CO2 was amnesic when tested 72 hr after training. The results of these experiments indicate that the administration of a nonamnesic dose of CYC immediately after training renders the memory susceptible to disruption by additional doses of CYC or other amnesic treatments for a longer period of time than normal. It is suggested that CYC delays consolidation and prolongs the labile period of memory formation.Flood and his associates have reported subsequent injections of low doses of ANI data which indicate that prolonging the pe-every 2 hr. They generally found that the riod of inhibition of cerebral protein syn-degree of memory impairment was a functhesis (CPS) after a learning experience by tion of the duration of continuous inhibition repeated posttraining injections of an anti-(> 80%) of CPS. Neither a single pretrainbiotic increases the severity of the memory ing injection of the low dose of ANI nor impairment. These investigators conclude posttraining injections without the prethat their data indicate that CPS occurring training injection produced a memory dechours after behavioral training is directly rement (Flood et al., 1973(Flood et al., ,1975a(Flood et al., , 1975b. involved in memory formation for the These data do seem to support the contraining experience (Flood, Bennett, Orme, tention that the prolonged inhibition of CPS & Rosenzweig, 1975a, 1975b Flood, Bennett, after training impairs memory by sup-Rosenzweig, & Orme, 1973).pressing memory-related protein synthesis The paradigm employed by the previous for long periods of time after training, researchers typically involved the adminis-However, they do not necessarily indicate tration of a subamnesic dose of anisomycin that specific, memory-related protein syn-(ANI) shortly before training, followed by thesis normally occurs several hours after training. If long-term memory formation This research was supported by Grant NS-12129-02 involves some metabolic process, which from the Nation...

Inhibition of cerebral protein synthesis does not prolong short-term memory.

“…Although we have reached a different conclusion than Quinton (1978), it is important to note that our results and those of Quinton are not contradictory. In Experiment 3, for example, mice treated with ANI (2 mg/animal) after an initial subamnestic dose of ANI (.5 mg/animal) demonstrated impaired retention 6 and 24 hr after training.…”

“…These experiments indicate that inhibition of brain protein synthesis by ANI does not prolong short-term memory. This contrasts with the suggestion of Quinton (1978) that inhibitors of brain protein synthesis decrease cerebral metabolism and thereby prolong short-term memory. The conclusion of this study, that short-term memory is not prolonged by inhibition of brain protein synthesis, was based on direct observations of forgetting as a function of the duration of protein synthesis inhibition.…”

“…In this experiment we examined the time course of forgetting after a single pretraining injection of either ANI (1 mg/animal) or physiological saline. Our drug treatment differs from the treatment given by Quinton (1978) in two respects. First, ANI rather than CYC was selected for use in this and subsequent experiments.…”

“…The first of these was based on reports that the PSI cycloheximide (CYC) disrupts short-term memory (Gutwein, Quartermain, & McEwen, 1974;Quartermain & McEwen, 1970;Rainbow, Adler, & Flexner, 1976;Randt, Barnett, McEwen, & Quartermain, 1971). The second was based on a report that CYC prolongs short-term memory (Quinton, 1978).…”

“…We have addressed the possibility suggested by Quinton (1978) that the PSIs prolong short-term memory. This suggestion was based on the finding that a nonamnestic dose of CYC (30 mg/kg) given immediately after training renders memory susceptible to disruption by a second injection of CYC (30 mg/kg) or to"a carbon dioxide treatment for an unusually long time after training.…”