Adult administration of peptides resulting in learning enhancement is not mediated through NMDA and GABA receptor expression

Abstract

IS NOT MEDIATED THROUGH NMDA AND GABA RECEPTOR EXPRESSION LAURA TOSO, ROBIN ROBERSON, DANIEL ABEBE, CATHERINE SPONG, National Institutes of Health (NIH), Unit on Perinatal and Develomental Neurobiology, NICHD&NIAAA, Bethesda, Maryland, National Institutes of Health (NIH), Unit on Perinatal and Develomental Neurobiology, Bethesda, Maryland OBJECTIVE: Administration of neurotrophic peptides NAPCSAL to aged mice resulted in significant learning enhancement (Toso 2006). NMDA and GABA receptors are fundamental for learning as they are the major modulators of the Long Term Potentiation, the electrophisiologic mechanism for learning. Also, these receptors have been shown to be involved in NAPCSAL prevention of learning deficit in a mouse model for fetal alcohol syndrome when administered prenatally during development(Toso 2006). Our objective was to test if NMDA and GABA receptors contribute to the learning enhancement induced by the peptides after adult administration. STUDY DESIGN: Aged (14.5 months) males were treated for 10 consecutive days with placebo or D-NAPCD-SAL (20mg, via gavage). At the end of the treatment brains were harvested. Calibrator-normalized relative real time PCR was performed using primers for GABA-Ab3, GABA-Aa5, NR2A and NR2B with GAPDH standardization. Statistical analysis included ANOVA with p!0.05 significant. RESULTS: 5 control brains and 6 brains from animals treated with NAPCSAL were collected. There was no difference in GABA-Ab3, GABAAa5, NR2A and NR2B subunits after adult administration of NAPCSAL as compared to the controls (pO0.05). CONCLUSION: Postnatal treatment with NAPCSAL induced learning enhancement in aged mice with mechanism that does not involve NMDA and GABA receptor expression. Treatment with the peptides does not acutely alter expression, although it may have an effect on the function of these receptors. Alternatively, the mechanism of learning enhancement may differ when administered to a developing fetus vs an adult.