Agents that affect cAMP levels or protein kinase a activity modulate memory consolidation when injected into rat hippocampus but not amygdala

Abstract

Male Wistar rats were trained in one-trial step-down inhibitory avoidance 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 hippocampus; 0 and 3 h for those implanted into the amygdala), these animals received microinfusions of SKF38393 (7.5 μg/side); SCH23390 (0.5 μg/side), norepinephrine (0.3 μg/side), timolol (0.3 μg/side), 8-OH-DPAT (2.5 μg/side), NAN-190 (2.5 μg/side), forskolin' (0.5 μg/side), KT5720 (0.5 μg/side) or 8-Br-cAMP (1.25 μg/side). Rats were tested for retention 24 h after training. When given into the hippocampus 0 h post-training, norepmephrine enhanced memory whereas KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post- training, 8-BrcAMP, forskolin, SKF38393, norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OHDPAT caused retrograde amnesia. Again, 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 cause any significant effect. These data suggest that in the hippocampus, but not in the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h after training, which is regulated by D1, β, and 5HT1A receptors. This correlates with data on increased 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 training in this task. These results suggest that the hippocampus, but not the amygdala, is involved in long-term storage of step-down inhibitory avoidance in the rat.