Centrally administered cycloheximide in rats: Behavioural concomitants and modulation of amnesic effects by biogenic amines

The behavioural consequences of centrally administered cycloheximide (400 μg, intraventricularly) were examined at various times after the injection and compared with the degree of protein synthesis inhibition. Operant behaviour (FR3 responding for water reward) was significantly depressed at 1, 2, 4, 6, 8, 10 and 12 hr after the injection but not at 24 hr, while general locomotor activity was significantly depressed at all time points except 1 and 24 hr. Amnesia for a passive avoidance response was observed when the cycloheximide was administered 1, 3, 5, 7, and 9 hr before the training trial but not at 11 or 17 hr. Protein synthesis was found to be maximally inhibited (80%) at 1 and 2 hr, moderately inhibited (60%) at 4, 6, and 8 hr, less but still significantly inhibited (40%) at 12 hr and slightly elevated (15%) at 24 hr after the central injection of cycloheximide. Posttraining administration of 1-tryptophan (100 mg/kg) or corticosterone (5 mg/kg) significantly reversed the amnesia produced by a central injection of cycloheximide given 5 hr before training, while imipramine (5 mg/kg), d-amphetamine (5 mg/kg) and hydrocortisone (5 mg/kg) were without significant effect. These results suggest that the disruption of passive avoidance memory by centrally administered cycloheximide may not be related to the inhibition of synthesis of memory-specific protein, but rather to a depression of central levels of biogenic amines, particularly serotonin. © 1977.