Figure 4.

Drugs that enhance the cAMP signaling pathway attenuate both the L-LTP and spatial memory defects in aged C57BL/B6 mice. (A) 6-Bromo-ApB application paired with four train stimulation (n = 5) significantly enhanced L-LTP in slices from 18-mo-old mice compared with tetanus only (n = 5) (main effect drug F_1,8 = 25.1, P < 0.001). 6-Bromo-ApB applied alone to slices from 18-mo-old mice had no effect on baseline values. 6-Bromo-ApB application paired with four train stimulation (n = 5) had no effect on L-LTP in slices from 3-mo-old mice compared with tetanus only (n = 5) (main effect of drug F_1,8 = 0.0054, P > 0.05). (B) SKF 38393 application paired with four train stimulation (n = 6) significantly enhanced L-LTP in slices from 18-mo-old mice compared with tetanus only (n = 5) (main effect of drug F_1,9 = 10.9, P = 0.0092). (C) Percentage of 18-mo-old mice receiving saline (n = 31), 3 (n = 13), 6 (n = 18) or 10 (n = 8) mg/kg SKF 38393 that acquired the spatial version of the Barnes maze. (D) SKF 38393 significantly decreased the number of errors made by 18-mo-old mice (main effect drug F_4,58 = 2.788, P = 0.0471). Mice receiving 6 mg/kg SKF 38393 were significantly different from mice receiving saline. (E) Percentage of 18-mo-old mice receiving vehicle (n = 10) or 0.05 μM (n = 10) rolipram that acquired the spatial version of the Barnes maze. (F) Rolipram significantly decreased the number of errors made by 18-mo-old mice (t = 2.204, P = 0.041).