Effects of Acetoxycycloheximide on Appetitive Learning and Memory

Abstract

The effects of direct brain infusions of acetoxycycloheximide (an inhibitor of protein synthesis; ACXH) on acquisition, storage and recall of memory for one-trial appetitive learning were examined in five experiments. ACXH was infused into the rats' hippocampi through implanted cannulas. Control subjects received an equal volume of physiological saline. ACXH was infused (a) 5 h before acquisition, (b) 5 hr before commencement of recall tests, and (c) immediately after acquisition. Each subject's general motor activity was recording during testing. The results indicate that (1) ACXH has similar effects on appetitive and avoidance learning. (2) ACXH administered immediately after acquisition, has no effect on memory. (3) At 4 hr after acquisition memory is affected by ACXH. (4) Short-term memory is unaffected by ACXH and can exist independently of long-term memory. (5) ACXH consistently reduces general motor activity.

Protein synthesis and memory: A review.

“…4. When performance is measured at days or weeks after training, retention is significantly impaired (Agranoff, 1968;Daniels, 1971Daniels, , 1972Davis, Spanis, & Squire, 1976;Davis et al, 1978;Flood, Rosenzweig, Bennett, & Orme, 1974;Flood et al, 1972Flood et al, , 1975aGibbs & Ng, 1977;Mark & Watts, 1971;Peterson & Squire, 1977;Rose, Gibbs, & Hambly, 1980;. 5.…”

Evolution and Resolution of Long-term Cardiac Memory

“…21,22 The process is common to complex mammalian life forms as well as to far simpler organisms such as aplysia. Neuroscientists have relied on cyclo-heximide as an inhibitor of new protein synthesis, 23,24 using it to differentiate the mechanisms responsible for long-term memory (requiring new protein synthesis) and those responsible for short-term memory (dependent on channel phosphorylation). 22 The dose of cycloheximide we used was derived from experience by others in the dog 4 and from our own preliminary dose-ranging experiments in rat and dog (data not reported).…”

“…Although we did not measure any independent descriptor of new protein synthesis, the literature clearly provides evidence for the expectation of its inhibition. 23,24 When cycloheximide was administered, the evolution of memory was significantly delayed. Moreover, as shown in Fig 9, both the effect of cycloheximide and the recovery from its effect were reproducibly demonstrable in the same animal.…”

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

“…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.…”

“…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.…”