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1.
Neuroscience ; 497: 73-85, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35752429

RESUMO

Oxytocin (OT) and vasopressin (AVP) are two closely related neuropeptides implicated in learning and memory processes, anxiety, nociception, addiction, feeding behavior and social information processing. Regarding learning and memory, OT has induced long-lasting impairment in different behaviors, while the opposite was observed with AVP. We have previously evaluated the effect of peripheral administration of OT or its antagonist (AOT) on the inhibitory avoidance response of mice and on the modulation of cholinergic mechanisms. Here, we replicate and validate those results, but this time through central administration of neuropeptides, considering their poor passage through the blood-brain barrier (BBB). When we delivered OT (0.10 ng/mouse) and its antagonist (0.10 ng/mouse) through intracerebroventricular (ICV) injections, the neuropeptide impaired and AOT enhanced the behavioral performance on an inhibitory avoidance response evaluated 48 h after training in a dose-dependent manner. On top of that, we investigated a possible central interaction between OT and the cholinergic system. Administration of anticholinesterases inhibitors with access to the central nervous system (CNS), the activation of muscarinic acetylcholine (Ach) receptors and the increase of evoked ACh release using linopirdine (Lino) (3-10 µg/kg, IP), reversed the impairment of retention performance induced by OT. Besides, either muscarinic or nicotinic antagonists with unrestricted access to the CNS reduced the magnitude of the performance-facilitating effect of AOT's central infusion. We suggest that OT might induce a cholinergic hypofunction state, resulting in an impairment of IA memory formation, a process for which the cholinergic system is crucially necessary.


Assuntos
Ocitocina , Receptores de Ocitocina , Aprendizagem , Memória , Antagonistas Nicotínicos/farmacologia , Ocitocina/farmacologia , Receptores Muscarínicos
2.
Neurobiol Learn Mem ; 185: 107534, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34619364

RESUMO

The ability to make predictions based on stored information is a general coding strategy. A prediction error (PE) is a mismatch between expected and current events. Our memories, like ourselves, are subject to change. Thus, an acquired memory can become active and update its content or strength by a labilization-reconsolidation process. Within the reconsolidation framework, PE drives the updating of consolidated memories. In the past our lab has made key progresses showing that a blockade in the central cholinergic system during reconsolidation can cause memory impairment, while reinforcement of cholinergic activity enhances it. In the present work we determined that PE is a necessary condition for memory to reconsolidate in an inhibitory avoidance task using both male and female mice. Depending on the intensity of the unconditioned stimulus (US) used during training, a negative (higher US intensity) or positive (lower US intensity/no US) PE on a retrieval session modified the behavioral response on a subsequent testing session. Furthermore, we demonstrated that the cholinergic system modulates memory reconsolidation only when PE is detected. In this scenario administration of oxotremorine, scopolamine or nicotine after memory reactivation either enhanced or impaired memory reconsolidation in a sex-specific manner.


Assuntos
Neurônios Colinérgicos/fisiologia , Consolidação da Memória , Animais , Aprendizagem da Esquiva/fisiologia , Neurônios Colinérgicos/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Feminino , Masculino , Consolidação da Memória/efeitos dos fármacos , Consolidação da Memória/fisiologia , Camundongos , Nicotina/farmacologia , Oxotremorina/análogos & derivados , Oxotremorina/farmacologia , Receptores Colinérgicos/efeitos dos fármacos , Receptores Colinérgicos/fisiologia , Escopolamina/farmacologia
3.
Neurobiol Learn Mem ; 177: 107360, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33307182

RESUMO

Over the years, experimental and clinical evidence has given support to the idea that acetylcholine (Ach) plays an essential role in mnemonic phenomena. On the other hand, the Hippocampus is already known to have a key role in learning and memory. What is yet unclear is how the Ach receptors may contribute to this brain region role during memory retrieval. The Ach receptors are divided into two broad subtypes: the ionotropic nicotinic acetylcholine receptors and the metabotropic muscarinic acetylcholine receptors. Back in 2010, we demonstrated for the first time the critical role of hippocampal α7 nicotinic acetylcholine receptors in memory reconsolidation process of an inhibitory avoidance response in mice. In the present work, we further investigate the possible implication of hippocampal muscarinic Ach receptors (mAchRs) in this process using a pharmacological approach. By specifically administrating agonists and antagonists of the different mAchRs subtypes in the hippocampus, we found that M1 and M2 but not M3 subtype may be involved in memory reconsolidation processes in mice.


Assuntos
Hipocampo/fisiologia , Consolidação da Memória/fisiologia , Receptores Muscarínicos/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Hipocampo/efeitos dos fármacos , Masculino , Consolidação da Memória/efeitos dos fármacos , Camundongos , Agonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/farmacologia , Oxotremorina/análogos & derivados , Oxotremorina/farmacologia , Pirenzepina/farmacologia , Receptores Muscarínicos/efeitos dos fármacos , Escopolamina/farmacologia , Succinato de Solifenacina/farmacologia
4.
Physiol Behav ; 171: 192-198, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28069463

RESUMO

Pre-training administration of scopolamine (SCP) resembles situations of cholinergic dysfunction, leading to memory impairment of mice trained in an inhibitory avoidance task. We suggest here that SCP does not impair memory formation, but acquisition is affected in a way that reduces the strength of the stored memory, thus making this memory less able to control behavior when tested. Hence, a memory trace is stored, but is poorly expressed during the test. Although weakly expressed, this memory shows extinction during successive tests, and can be strengthened by using a reminder. Our results indicate that memories stored under cholinergic dysfunction conditions seem absent or lost, but are in fact present and experience common memory processes, such as extinction, and could be even recovered by using appropriate protocols.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Antagonistas Colinérgicos/toxicidade , Extinção Psicológica/fisiologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/fisiopatologia , Escopolamina/toxicidade , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrochoque/efeitos adversos , Extinção Psicológica/efeitos dos fármacos , Masculino , Camundongos , Tempo de Reação/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia
5.
Neurobiol Learn Mem ; 133: 79-88, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27321160

RESUMO

Persistence is an attribute of long-term memories (LTM) that has recently caught researcher's attention in search for mechanisms triggered by experience that assure memory perdurability. Up-to-date, scarce evidence of relationship between reconsolidation and persistence has been described. Here, we characterized hippocampal ERK participation in LTM reconsolidation and persistence using an inhibitory avoidance task (IA) at different time points. Intra-dorsal-hippocampal (dHIP) administration of an ERK inhibitor (PD098059, PD, 1.0µg/hippocampus) 3h after retrieval did not affect reconsolidation of a strong IA, when tested 24h apart. However, the same manipulation impaired performance when animals were tested at 7d, regardless of the training's strength; and being specific to memory reactivation. To the best of our knowledge, this is the first report showing that persistence might be triggered after memory reactivation involving an ERK/MAPK-dependent process.


Assuntos
Aprendizagem da Esquiva/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hipocampo/metabolismo , Consolidação da Memória/fisiologia , Memória de Longo Prazo/fisiologia , Rememoração Mental/fisiologia , Inibidores de Proteínas Quinases/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Flavonoides/administração & dosagem , Flavonoides/farmacologia , Hipocampo/efeitos dos fármacos , Consolidação da Memória/efeitos dos fármacos , Memória de Longo Prazo/efeitos dos fármacos , Rememoração Mental/efeitos dos fármacos , Camundongos , Inibidores de Proteínas Quinases/administração & dosagem , Fatores de Tempo
6.
Neuroscience ; 294: 227-37, 2015 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-25791227

RESUMO

Reconsolidation has been defined as the process of memory stabilization after retrieval involving, among others, gene expression regulation and post-translational modifications. Many of these mechanisms are shared with memory consolidation. Here, we studied hippocampal ERK participation on memory reconsolidation of an inhibitory avoidance task in CF-1 mice. We found a retrieval-induced cytosolic ERK2 activation in the hippocampus (HIP) 15 min after memory reactivation, and an inhibition at 45 min. PD098059, a MEK1/2 (MAPK/ERK kinase) inhibitor, administered in the HIP immediately after retrieval impaired memory in a dose-dependent fashion. However, infusions of the highest dose of PD098059 performed 40 min after retrieval enhanced memory in mice trained with a weaker footshock. These results suggest for the first time that ERK2 is involved in memory reconsolidation in a biphasic fashion. Furthermore, the inhibition of ERK could either impair or enhance mice performance depending on ERK state of activation.


Assuntos
Aprendizagem da Esquiva/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Memória/fisiologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Animais , Hipocampo/metabolismo , Masculino , Camundongos , Fosforilação
7.
J Physiol Paris ; 108(4-6): 286-91, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24819880

RESUMO

Central cholinergic system is critically involved in all known memory processes. Endogenous acetylcholine release by cholinergic neurons is necessary for modulation of acquisition, encoding, consolidation, reconsolidation, extinction, retrieval and expression. Experiments from our laboratory are mainly focused on elucidating the mechanisms by which acetylcholine modulates memory processes. Blockade of hippocampal alpha-7-nicotinic receptors (α7-nAChRs) with the antagonist methyllycaconitine impairs memory reconsolidation. However, the administration of a α7-nAChR agonist (choline) produce a paradoxical modulation, causing memory enhancement in mice trained with a weak footshock, but memory impairment in animals trained with a strong footshock. All these effects are long-lasting, and depend on the age of the memory trace. This review summarizes and discusses some of our recent findings, particularly regarding the involvement of α7-nAChRs on memory reconsolidation.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Colinérgicos/metabolismo , Colinérgicos/farmacologia , Memória/efeitos dos fármacos , Neurofarmacologia , Animais , Sistema Nervoso Central/metabolismo , Humanos , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
8.
Neurobiol Learn Mem ; 98(2): 112-21, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22776591

RESUMO

It is widely known that pre-training systemic administration of the muscarinic antagonist scopolamine (SCP) (0.5mg/kg, i.p.) leads to anterograde memory impairment in retention tests. The administration of the α(7)-nicotinic receptor agonist choline (Ch) in the dorsal hippocampus (0.8µg/hippocampus) immediately after memory reactivation allowed recovery from scopolamine-induced memory impairment. This effect of Ch was time-dependent, and retention performance was not affected in drug-treated mice that were not subjected to memory reactivation, suggesting that the performance effects are not due to non-specific effects of the drug. The effects of Ch also depended on the age of the reactivated memory. Altogether, our results suggest that Ch exerts its effects by modulating memory reconsolidation, and that the memory impairment induced by low doses of SCP is a memory expression failure and not a storage deficit. Therefore, reconsolidation, among other functions, might serve to change memory expression in later tests. Summarizing, our results open new avenues about the behavioral significance and the physiological functions of memory reconsolidation, providing new strategies for recovering memories from some types of amnesia.


Assuntos
Colina/farmacologia , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Agonistas Nicotínicos/farmacologia , Nootrópicos/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Hipocampo/fisiologia , Masculino , Transtornos da Memória/induzido quimicamente , Camundongos , Antagonistas Muscarínicos/farmacologia , Retenção Psicológica/efeitos dos fármacos , Escopolamina/farmacologia , Fatores de Tempo
9.
Behav Brain Res ; 220(2): 319-24, 2011 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-21333692

RESUMO

Intracellular levels of the second messengers cAMP and cGMP are maintained through a balance between production, carried out by adenyl cyclase (AC) and guanylyl cyclase (GC), and degradation, carried out by phosphodiesterases (PDEs). Recently, PDEs have gained increased attention as potential new targets for cognition enhancement, with particular reference to phosphodiesterase type 5 (PDE5A). It is accepted that once consolidation is completed memory becomes permanent, but it has also been suggested that reactivation (memory retrieval) of the original memory makes it sensitive to the same treatments that affect memory consolidation when given after training. This new period of sensitivity coined the term reconsolidation. Sildenafil (1, 3, and 10mg/kg, ip), a cGMP-PDE5 inhibitor, facilitated retention performance of a one-trial step-through inhibitory avoidance task, when administered to CF-1 male mice immediately after retrieval. The effects of sildenafil (1mg/kg, ip) were time-dependent, long-lasting and inversely correlated with memory age. The administration of sildenafil (1mg/kg, ip) 30 min prior to the 2nd retention test did not affect retention of mice given post-retrieval injections of either vehicle or sildenafil (1mg/kg, ip). Finally, an enhancement of retention was also observed in CF-1 female mice receiving sildenafil (1mg/kg, ip) immediately, but not 180 min after retrieval. In the present paper we reported for the first time that systemic administration of sildenafil after memory reactivation enhances retention performance of the original learning. Our results indirectly point out cGMP, a component of the NO/cGMP/PKG pathway, as a necessary factor for memory reconsolidation.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Memória/efeitos dos fármacos , Inibidores da Fosfodiesterase 5/farmacologia , Piperazinas/farmacologia , Sulfonas/farmacologia , Fatores Etários , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletrochoque/efeitos adversos , Feminino , Masculino , Camundongos , Purinas/farmacologia , Retenção Psicológica/efeitos dos fármacos , Citrato de Sildenafila , Estatísticas não Paramétricas , Fatores de Tempo
10.
Physiol Behav ; 102(3-4): 332-7, 2011 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21118701

RESUMO

Subjects exposed to learning experiences could store the new information through memory consolidation process. If consolidation is interfered by exposing the experimental subjects to another novel stimulus, memory of the first learning situation is sometimes disrupted. The cholinergic system is critically involved in acquisition of new information. Here, we use low doses of the muscarinic cholinergic receptor antagonist scopolamine (SCOP) to disrupt acquisition of new information, but sparing memory consolidation of previous memories. Mice were consecutively exposed to two learning situations: the inhibitory avoidance (IA) and the nose-poke habituation (NPH) tasks. The exposure of mice to the NPH task, after being trained in the IA apparatus, impairs consolidation of the avoidance memory in a manner related to the duration of the exposure to the NPH task. If the exposure to the NPH task occurred after reactivation of the avoidance memory, reconsolidation was impaired. Blockade of acquisition of the NPH task by SCOP allowed consolidation and reconsolidation of the avoidance memory. Results indicate that cholinergic system blockade by SCOP impairs acquisition but is less able to affect memory consolidation. The mere exposure and perception of a novel situation are not sufficient conditions to cause impairment of retention performance about previously learned information, but effective processing leading to acquisition of the NPH task information is necessary to cause the interference between both learning situations.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Habituação Psicofisiológica/efeitos dos fármacos , Memória/efeitos dos fármacos , Antagonistas Muscarínicos/farmacologia , Escopolamina/farmacologia , Análise de Variância , Animais , Masculino , Camundongos , Estatísticas não Paramétricas
11.
Neuroscience ; 171(2): 531-43, 2010 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-20832455

RESUMO

CF-1 male mice were trained in an inhibitory avoidance (IA) task using either a mild or a high footshock (0.8 or 1.2 mA, 50 Hz, 1 s). A retention test was given 48 h later. Immediately after the retention test, mice were given intra-dorsal hippocampus infusions of either choline (Ch, an α7 nicotinic acetylcholine receptor (α7nAChR) agonist, 0.08-1.30 µg/hippocampus), or methyllycaconitine (MLA, an α7nAChR antagonist, 1.0-30.0 µg/hippocampus). Memory retention was tested again 24 h later. Methyllycaconitine impaired retention performance regardless of footshock intensity and its effects were long lasting. Ch impaired retention performance only in those mice trained with a high footshock. On the contrary, Ch enhanced retention performance when mice were trained with a mild footshock. These effects were long lasting and dose- and time-dependent. Retention performance was not affected in drug-treated mice that were not subjected to memory reactivation, suggesting that the performance effects could not be attributable to non-specific effects of the drugs. Methyllycaconitine effects were dose-dependently reversed by choline, suggesting that MLA and Ch interact at the α7nAChR. Altogether, results suggest that hippocampal α7nAChRs play a critical role in reconsolidation of an IA response in mice, and may also have important implications for dynamic memory processes. This is the first presentation, to our knowledge, indicating that a specific receptor (α7nAChR) is able to modulate consolidated memories after retrieval.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Receptores Nicotínicos/fisiologia , Aconitina/análogos & derivados , Aconitina/farmacologia , Animais , Colina/farmacologia , Hipocampo/metabolismo , Inibição Psicológica , Masculino , Camundongos , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Receptor Nicotínico de Acetilcolina alfa7
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