Effects of aripiprazole on radial-arm maze learning deficits in rats subjected to chronic neonatal treatment with MK-801

UEHARA J.M.; BIN ISMAIL M.A.; YAMADA K.; ICHITANI Y.

Tsukuba

Congreso; Tsukuba Global Science Week; 2017

University of Tsukuba

N-methyl-D-aspartate (NMDA) receptors are a major subtype of ionotropic glutamate receptors implicated in long-term potentiation (LTP), the neural process underlying learning and memory. Previous studies conducted in rodents indicate that repeated neonatal treatment with NMDA receptor antagonists produces long-term cognitive impairments in adulthood. However, the ability of current antipsychotics to reduce these deficits has not been thoroughly addressed. We investigated the effects of aripiprazole on spatial learning and working memory ability of adult rats neonatally treated with the non-competitive antagonist MK-801 (dizocilpine; 5-methyl-10, 11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine), using the radial-arm maze. In line with previous results, chronic neonatal administration of MK-801 (0.5 mg/kg s.c., twice daily) significantly delayed learning of the task, regardless of the pharmacological treatment given during adulthood. However, training extended for 40 trialsallowed almost all MK-801-treated animals to reach the learning criterion. Notably, injections of 0.5 mg/kg aripiprazole (i.p.) given before each behavioral trial significantly decreased the trials required to learn the task in the MK-801 group, while a higher dose of 1.0 mg/kg did not produce any improvements. These findings suggest that chronic blockade of NMDA receptors during an early critical period significantly delays - but does not prevent - spatial learning by impairing working memory in adulthood. Improvements shownby the administration of the atypical antipsychotic aripiprazole may provide predictive validity for this animal model.