Effect of age of habit on susceptibility to cycloheximide-induced amnesia in mice.

Abstract

The amnesic effects of cycloheximide (CYC) on habits of different ages were investigated in a food-motivated, discrimination-reversal task. Groups of C57BL/6J mice were injected 30 min before training or immediately, 3 days, 6 days, or 9 days after training. Retention was tested 24 hr after CYC treatment. The usual amnesic effect of CYC occurred in animals injected before training. No amnesia was apparent in groups injected immediately, 3 days, or 9 days after training. However, a reliable and reproducible amnesia occurred in the group injected 6 days after training. This amnesia could be reversed by pretest treatment with a monoamine oxidase inhibitor, pheniprazine. Pheniprazine, given 7 days after training, also enhanced retrieval of memory in saline-injected mice.Although amnesia can sometimes result from posttraining injections of cycloheximide (CYC) or acetoxycycloheximide (AXM) (e.g., Geller, Robustelli, Barondes, Cohen, & Jarvik, 1969;Quartermain & McEwen, 1970), the majority of experiments employing multiple-trial tasks failed to demonstrate amnesia when CYC or AXM is given after training (e.g., Barondes & Cohen, 1967;Daniels, 1972;Flexner & Flexner, 1966;Squire & Barondes, 1972). These findings have led to a general acceptance of the notion that protein synthesis must be inhibited while learning is taking place in order for an impairment in memory to be subsequently demonstrated.The ineffectiveness of posttraining CYC treatment in multiple-trial tasks is most commonly accounted for by reference to the consolidation hypothesis. Briefly, this hypothesis assumes that by the time the training trials are terminated, or shortly thereafter, the memory trace has consolidated into a storage stage (either intermediate or long-term memory), which is no longer susceptible to disruption by protein-synthesis inhibition (McGaugh, 1966(McGaugh, , 1968). An alter-This study was supported by Grant Foundation, Incorporated. We thank G. B. Whitfleld of the Upjohn Company forsupplying the cycloheximide.Requests for reprints should be sent to David

Studies on memory: inhibitors of protein synthesis also inhibit catecholamine synthesis.

“…In view of our failure to find any abnormality at 24 hr after injection of CXM, we would have expected return of memory at this time. With AMPT, transient amnesia has also been observed 24 hr after treatment (18), at a time when we found no evidence of its characteristic biochemical effect. Perhaps all of these agents have prolonged effects on certain critical areas of brain obscured by our use of the whole cerebral hemispheres.…”

“…The first measurement may be insensitive to changes in CA synthetic rate, while in the second no assessment was made of the effects of (4)(5)(6). CXM, for example, causes amnesia, not due to illness (18), 24 hr after administration, with recovery of memory 1 day later (5). In view of our failure to find any abnormality at 24 hr after injection of CXM, we would have expected return of memory at this time.…”

The many faces of amnesia

“…When viewed with evidence that epinephrine levels are typically high after inhibitory avoidance training during the shorter temporal gradient (McCarty and Gold 1981), the findings suggest that hormonal status at the time of amnestic treatment is an important variable. Or, perhaps changes in hormonal response to memory tests presented after forgetting has begun underlie observations that cycloheximide can impair memory (Quartermain and Botwinick 1975) and that amphetamine or electrical stimulation of the midbrain reticular formation can enhance retrieval of partially forgotten memories (Sara et al 1980;Quartermain et al 1988). These findings raise the possibility that decreases as well as increases in hormonal responses elicited by reinstatement conditions may modulate the ability of treatments to influence memory long after the initial experience.…”

“…Modulators are most likely to enhance memories for recent events that are otherwise weakly remembered. Also, weak memories may be more susceptible than are strong memories to modulation of cognitive reorganization after new related information is presented (e.g., Quartermain and Botwinick 1975;Sara et al 1980;Quartermain et al 1988;Suzuki et al 2004).…”