Abstract: AIM: To observe the effects of rapamycin pregnancy intervention on cognitive function of autism model in rat offspring.  METHODS: Fourteen pregnant rats were randomly divided into normal group (n=3), model group (n=4), rapamycin (RAPA) control group (n=3) and intervention group (n=4). The model group and intervention group were i.p. injected with sodium valproate 600 mg/kg at embryonic day (E) 12.5 to establish autism model in rat offspring. RAPA control group and intervention group were i.g. given RAPA 4 mg/kg every day from the 13th day of gestation until the offspring rats were weaned at 23 days. After the birth of the above four groups of pregnant rats, 15, 27, 21 and 26 offspring male rats were selected to conduct behavioral tests to identify the model. Then, paw withdrawal mechanical threshold (PWMT), tail flick latency (TFL) evoked under different light intensity and learning and memory function of offspring rats were further detected. RESULTS: Rat offspring in the model group had lower growth and development indexes and exploratory behavior ability, but stronger repetitive stereotyped behavior compared with the normal group (P<0.05), while the indexes between the intervention group and model group were reversed (P<0.05). The model group had higher PWMT than normal group (P<0.01) and the PWMT of intervention group was lower than that of model group (P<0.01). The TFLs of rats in 4 groups showed a timed dose-response relationship (TDRR, P<0.01), that is, TFLs were shortened with the increase of light intensity. The TDRR curve of model group shifted to right compared with normal group (P<0.01) and intervention group shifted to left compared with model group (P<0.01). At the light intensity of Focus 34, 51 and 76, the TFLs of model group were longer than those of normal group (P<0.01) and intervention group had shorter TFLs compared with model group (P<0.01). In spatial probing trial of Morris water maze test, the platform crossover number in model group was less than that in normal group (P<0.01) and that in intervention group was more than model group (P<0.05). CONCLUSION: RAPA intervention during pregnancy may alleviate behavior disorder, pain tolerance and memory function of autism model in rat offspring to some extent.

Key words: autism, rapamycin, pain, timed dose-response relationship, learning and memory function