Pharmacological effects of agmatine on the reference and working memory functions in adult rats prenatally exposed to valproic acid

Background and Aim : Evidence indicates that NMDA receptor agonists improve memory performance in adult rats prenatally exposed to valproic acid. In previous studies, the effect of them on the memory has been assessed in procedures that may also be influenced by motivational or motor factors, both of which occur with NMDA antagonists. Therefore, usage of the procedures that differ in motivation and vulnerability to effects of non-spatial factors, with a common reliance on memory, is required. There are no current reports on the autism model of rats tested in the radial-arm maze (RAM) and also NMDA antagonists effects on variables of it.Methods : The autism was modeled in rats by subcutaneous (SC) administration of valproic acid (600mg/kg) to pregnant rats at the gestational day 12.5. Autism-associated behaviors in male offsprings were tested in an open field test (OFT) and three-chambered test (TCT) on postnatal day 50, and the animals were trained in an eight-arm radial maze task until the rats attained the criteria of 80 % correct choice in the five consecutive trials. Twenty-four hours after criteria meeting, agmatine (40 mg/kg, SC) was injected 30 min before the behavioral tests including OFT, TCT, and memory phase of the RAM.Results : We reported that agmatine rescued social deficits, anxiety-related behavior in VPA-treated rats. Prenatally VPA treatment did not influence the number of days to achieve the trained criteria and reference memory error (RME); however, by the mid of training, VPA-treated rats made significantly more WME. There was no significant difference for RME, WME, and total error between the groups after agmatine injection (p > 0.05).Conclusion : Our results showed that VPA and control rats showed the same manner in the RAM task, and acute injection of agmatine rescued social and anxiety-like behavior without the effect on RAM.

Keywords:

Autism , Valproic acid , Agmatine , NMDA antagonist , Radial- arm maze