Angiotensin II blocks memory consolidation through an AT2 receptor-dependent mechanism.
OBJECTIVE
Several studies suggest that the brain renin-angiotensin system is involved in memory consolidation. However, the participation of angiotensin II (AII) in this process is controversial. This is probably due to the fact that many of the studies carried out to elucidate this matter employed multitrial learning paradigms together with pretraining intracerebroventricular infusions, and therefore were unable to distinguish between consolidation and retrieval related events and lacked anatomical specificity. To circumvent this problem, we analyzed the role played in memory consolidation by AII using the hippocampal-dependent, one-trial, step-down inhibitory avoidance task (IA) in combination with stereotaxically localized intrahippocampal infusion of drugs.


RESULTS
Rats bilaterally implanted with infusion cannulae into the CA1 region of the dorsal hippocampus (CA1) were trained in IA and tested for memory retention 24 h later. We found that when infused into CA1 immediately or 30 min after training but not later, AII produced a dose-dependent amnesic effect without altering locomotor activity, exploratory behavior or anxiety state. The amnesic effect of AII was not mimicked by angiotensin IV (AIV) and was totally blocked by the AII-type 2 receptor (AT2) antagonist, PD123319, but not by the AII-type 1 receptor (AT1) antagonist, losartan. Importantly, when infused alone, neither PD123319 nor losartan produced any effect on memory retention.


CONCLUSIONS
Our data indicate that, when given into CA1, AII blocks memory formation through a mechanism involving activation of AT2 receptors; however, endogenous AII does not seem to participate in the consolidation of IA long-term memory.
Kerr
Daniel S
DS
Center for Memory Research, ICBS, Department of Biochemistry, Federal University of Rio Grande do Sul, Ramiro Barcelos 2600-Anexo, Porto Alegre, 90035-003, Brazil.
Bevilaqua
Lia R M
LR
Bonini
Juliana S
JS
Rossato
Janine I
JI
Köhler
Cristiano A
CA
Medina
Jorge H
JH
Izquierdo
Iván
I
Cammarota
Martín
M
D000647:Amnesia / Q000139:chemically induced / Q000378:metabolism; D000804:Angiotensin II / Q000008:administration & dosage* / Q000633:toxicity; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists* / Q000502:physiology*
D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319