Age dependent effects of 5-hydroxytryptamine upon memory consolidation and cerebral protein synthesis

The data from the series of experiments generally supported the view that inhibition of protein synthesis may be effected by increases in the regional concentration of 5-HT, and under circumstances wherein such increases are precluded either because of endogenous metabolic circumstances or tissue uptake properties, protein synthesis inhibition may not occur.

Abstract

In four experiments consideration was given to the effect of intracranially administered 5-Hydroxytryptamine (5-HT) upon several age dependent cerebral processes. These included (1) the tissue uptake of exogenously administered intracranial 5-HT, which in 17-day old CF-IS strain mice did not lead to increases in forebrain 5-HT level; (2) when administered in close temporal proximity with a single trial passive avoidance training trial, intracranial 5-HT produced a significant degree of retrograde amnesia in 15, 20, and 30-day-old mice, with a temporal gradient for this amnesic effect measured out to eight min. No significant retrograde amnesic effect for such passive avoidance behavior was produced in 17-day old animals. The amnesic effect appeared to be specific to 5-HT, in that (3) other amines or 5-HT analogs administered intracranially in equimolar concentration, had no amnesic effect. The relationship between age and the effect of intracranially administered 5-HT was considered with regard to regional cerebral protein synthesis. The incorporation of radioactive leucine into proteins of several regions of the brain, including cerebral cortex, basal ganglia and diencephalon, midbrain, and cerebellum, was significantly inhibited within 20 min following 5-HT administration. No significant inhibition of cerebral protein synthesis was observed in 17-day old mice of the same strain given identical treatment. The data from the series of experiments generally supported the view that inhibition of protein synthesis may be effected by increases in the regional concentration of 5-HT, and under circumstances wherein such increases are precluded either because of endogenous metabolic circumstances or tissue uptake properties, protein synthesis inhibition may not occur. Such was the case for the 17-day old CF-1S strain mouse wherein protein synthesis inhibition was attenuated and the retrograde amnesic effect of intracranial 5-HT was antagonized.