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 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 micrograms/side), SCH23390 (0.5 microgram/side), norepinephrine (0.3 microgram/side), timolol (0.3 microgram/side), 8-OH-DPAT (2.5 micrograms/side), NAN-190 (2.5 micrograms/side), forskolin (0.5 microgram/side), KT5720 (0.5 microgram/side) or 8-Br-cAMP (1.25 micrograms/side). Rats were tested for retention 24 h after training. When given into the hippocampus 0 h post-training, norepinephrine 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-Br-cAMP, forskolin, SKF38393, norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OH-DPAT 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, beta, 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.
Bevilaqua
L
L
Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Brasil.
Ardenghi
P
P
Schröder
N
N
Bromberg
E
E
Quevedo
J
J
Schmitz
P K
PK
Bianchin
M
M
Walz
R
R
Schaeffer
E
E
Medina
J H
JH
Izquierdo
I
I
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis*; D017362:Cyclic AMP Response Element-Binding Protein / Q000032:analysis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D001552:Benzazepines; D017362:Cyclic AMP Response Element-Binding Protein; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D009638:Norepinephrine