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

Abstract

Male Swiss albino CD-I mice given a single subcutaneous injection of a cerebral protein synthesis inhibitor, anisomycin (ANI; 1 mg/animal), 20 min prior to a single trial of passive avoidance training demonstrated impaired retention at tests given 3 hr, 6 hr, 1 day, and 7 days after training. Retention was not significantly different from that of saline controls when tests were given .5 or 1.5 hr after training. Prolonging inhibition of brain protein synthesis by giving either one or two additional injections of ANI at 2 hr or at 2 and 4 hr after training did not prolong good retention performance. The temporal development of impaired retention in ANI-treated mice could not be accounted for by drug dosage, duration of protein synthesis inhibition, or nonspecific sickness at test. In contrast to the suggestion that protein synthesis inhibition prolongs short-term memory, the results of this experiment indicate that short-term memory is not prolonged by antibiotic drugs that inhibit cerebral protein synthesis. All evidence seems consistent with the hypothesis that short-term memory is independent of protein synthesis and that the establishment of long-term memory depends on protein synthesis during or shortly after training.Inhibition of cerebral protein synthesis shortly before or after training markedly impairs long-term retention in a variety of tasks and species (Agranoff, 1971;Barondes, 1975;Barraco & Stettner, 1976;Flexner, Flexner, & Stellar, 1963). These findings suggest that cerebral protein synthesis is required for the formation of long-term memory. A cardinal feature of the amnesia induced by protein synthesis inhibitors (PSIs) is that there is no effect on either acquisition

Long-term working memory in the rat: Effects of hippocampally applied anisomycin.

“…It has also been suggested that tests conducted 6 hr after avoidance training reveal the functional integrity of LTM (e.g., Davis et al, 1981;Gibbs & Ng, 1977). We suggest that both of these conclusions are valid and not necessarily contradictory because working memory tested 6 hr after training may reflect function of its longterm component.…”

“…It has been shown that when rats are trained in the radial maze, they can retain information in working memory for up to 6 hr (Shavalia, Dodge, & Beatty, 1981) in the radial maze. It has also been suggested that tests conducted 6 hr after avoidance training reveal the functional integrity of LTM (e.g., Davis et al, 1981; Gibbs & Ng, 1977). We suggest that both of these conclusions are valid and not necessarily contradictory because working memory tested 6 hr after training may reflect function of its long-term component.…”

“…In studies on the role of protein synthesis in memory formation, it has been proposed that protein synthesis is not important for normal STM whereas the formation of new LTMs is protein synthesis dependent (e.g., Cohen & Barondes, 1968). This conclusion is supported by experiments involving not only passive and active avoidance learning with rodents (e.g., Cohen & Barondes, 1968;Davis, Rosenzweig, Jones, & Bennett, 1981) but also rodent appetitive learning (Daniels, 1972) and avian avoidance and appetitive learning (Gibbs & Ng, 1976. In these experiments, the temporal course of development of amnesia following the administration of specific classes of drugs is the main criteria for defining STM or LTM.…”

“…In addition, working memory and STM are thought to be more vulnerable to disruption than reference memory and LTM (Honig, 1978;Wagner, 1978). Therefore, we began assessing the functional significance of the temporal stages of memory function, as defined by investigators such as Davis et al (1981), by determining the effects of the protein synthesis inhibitor anisomycin (ANI) on working and reference memories. If the neurochemistry of working memory is analogous to STM, ANI should have no effect on retention of items stored in working memory.…”

Protein synthesis and memory: A review.

“…By this view, whether the short-term, protein synthesis-independent phase of memory is affected or unaffected by PSIs can be addressed directly by measuring how long memory persists after training. Davis, Rosenzweig, Jones, and Bennett (1981) assumed that if short-term memory were extended by a posttraining injection of a PSI, then such short-term memory should be capable of supporting performance for an extended time after training. Thus, the time course of forgetting following a single injection of ANI should be more rapid than following two injections of ANI given 2 hr apart.…”