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During the postnatal period, male Wistar rats were treated with orotate, either from the 6th to 15th, 16th to 25th, or 26th to 35th day of life. Learning and memory were tested in adulthood. Rats that received orotate from the 6th to 15th day showed a better retention of a learned brightness discrimination (Y-maze) than controls. An active avoidance (pole jumping) was learned more quickly by the rats orotate-treated from the 6th to 15th day than by controls. The spontaneous locomotor activity of previously orotate-treated rats was the same as in controls. Body weight measurements revealed no differences between orotate rats and control rats. The results suggest that memory retention in adulthood can be improved by postnatal orotate treatment.

The effect of methylglucamine orotate (MGO) on learning and memory was investigated in 24-month-old rats using brightness discrimination in a Y-chamber and active avoidance in a shuttle box. In both learning procedures, an improvement of memory retention following 5-day MGO treatment (225 mg/kg per day) was observed. The retention of untreated old animals was significantly lower compared to 8-week-old rats. MGO treatment resulted in a significant improvement of retention in old rats, which nearly compensated for their memory deficit.

The effects of methylglucamine orotate (MGO) were studied on polygraphic sleep recordings in rats for 8 h per day between 8 a.m. and 4 p.m. MGO (225 mg/kg) was injected intraperitoneally immediately prior to the onset of recording. In the acute experiment, the effect of MGO was compared to pre- and post-drug control days. In the chronic experiment, a sequence of 5 control days, 10 days of MGO treatment, and a further 8 control days was tested. Both acute and chronic administration of MGO resulted in increased paradoxical sleep (PS) latency and a small, but significant, decrease in PS during the first 4 h after injection. This effect seems to be specific to PS, as no effects of MGO on waking or total sleep were found. With chronic administration, no PS rebound occurred within the 8-h recording time during the 8-day post-treatment control period. How the RNA precursor can decrease PS and whether this effect may play a role in the memory-improving action of the substance is discussed in terms of an interrelationship between macromolecular synthesis, sleep, and memory, respectively.