AGENTS THAT AFFECT CAMP LEVELS OR PROTEIN-KINASE-A ACTIVITY MODULATE MEMORY CONSOLIDATION WHEN INJECTED INTO RAT HIPPOCAMPUS BUT NOT AMYGDALA

Male Wistar rats were trained in one-trial step-down inhibitory avoida nce using a 0.4-mA footshock. At various times after training (0, 1.5, 3, 6 and 9 h for the animals implanted into the CA1 region of the hip pocampus; 0 and 3 h for those implanted into the amygdala), these anim als received microinfusions of SKF38393 (7.5 mu g/side), SCH23390 (0.5 mu g/side), norepinephrine (0.3 mu g/side), timolol (0.3 mu g/side), 8-OH-DPAT (2.5 mu g/side), NAN-190 (2.5 mu g/side), forskolin (0.5 mu g/side), KT5720 (0.5 mu g/side) or 8-Br-cAMP (1.25 mu g/side). Rats we re tested for retention 24 h after training. When given into the hippo campus 0 h post-training, norepinephrine enhanced memory whereas KT572 0 was amnestic. When given 1.5 h after training, all treatments were i neffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, S KF38393; norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OH-DPAT caused retrograde amnesia. Aga in, at 9 h after training, all treatments were ineffective. When given into the amygdala, norepinephrine caused retrograde facilitation at 0 h after training. The other drugs infused into the amygdala did not c ause any significant effect. These data suggest that in the hippocampu s, but not in the amygdala, a cAMP/protein kinase A pathway is involve d in memory consolidation at 3 and 6 h after training, which is regula ted by D-1, beta, and 5HT1A receptors. This correlates with data on in creased post-training cAMP levels and a dual peak of protein kinase A activity and CREB-P levels (at 0 and 3-6 h) in rat hippocampus after t raining in this task. These results suggest that the hippocampus, but not the amygdala, is involved in long-term storage of step-down inhibi tory avoidance in the rat.