RESUMO
The participation of DNA methylation processes in the mechanisms of anterograde and retrograde amnesia caused by impaired reconsolidation of conditioned food aversion memory by NMDA glutamate receptor antagonists or serotonin receptor antagonists, respectively, were studied on grape snails. Anterograde amnesia was characterized by impaired formation of long-term memory during repeated learning. Administration of a DNA methyltransferase (DNMT) inhibitor to amnestic animals resulted in accelerated formation of long-term memory during 1 day of repetitive training vs 3 days during initial training. In serotonin-dependent retrograde amnesia, repeated learning without DNMT inhibitor administration or after inhibitor injections led to the formation of long-term memory. The dynamics of memory formation was similar in both cases and did not differ from that during the initial training: the memory was formed within 3 days of training. Thus, epigenetic processes of DNA methylation are selectively involved in the mechanisms of anterograde amnesia, but do not participate in the mechanisms of retrograde amnesia.
Assuntos
Amnésia Anterógrada , Animais , Metilação de DNA , Amnésia Retrógrada/genética , Amnésia/induzido quimicamente , Amnésia/genética , Inibidores Enzimáticos , Epigênese GenéticaRESUMO
The study of the amnesia mechanisms is of both theoretical and practical importance. The mechanisms of anterograde amnesia are the least studied, due to the lack of an experimental model that allows studying this amnesia type molecular and cellular mechanisms. Previously, we found that conditional food aversion memory reconsolidation impairment in snails by NMDA glutamate receptor antagonists led to the amnesia induction, in the late stages of which (>10 days) repeated training did not cause long-term memory formation. In the same animals, long-term memory aversion to a new food type was formed. We characterized this amnesia as specific anterograde amnesia. In the present work we studied the role of epigenetic DNA methylation processes as well as protein and mRNA synthesis in the mechanisms of anterograde amnesia and memory recovery. DNMT methyltransferase inhibitors (iDNMT: zebularine, RG108 (N-Phthalyl-1-tryptophan), and 5-AZA (5-Aza-2'-deoxycytidine)) were used to alter DNA methylation. It was found that in amnesic animals the iDNMT administration before or after shortened repeated training led to the rapid long-term conditional food aversion formation (Ebbinghaus saving effect). This result suggests that amnestic animals retain a latent memory, which is the basis for accelerated memory formation during repeated training. Protein synthesis inhibitors administration (cycloheximide) before or immediately after repeated training or administration of RNA synthesis inhibitor (actinomycin D) after repeated training prevented memory formation under iDNMT action. The earlier protein synthesis inhibitor effect suggests that the proteins required for memory formation are translated from the pre-existing, translationally repressed mRNAs. Thus, we have shown for the first time that the anterograde amnesia key mechanism is DNMT-dependent suppression of the transcription of genes involved in memory mechanisms. Inhibition of DNMT during repeated training reversed these genes expression blockade, opening access to them by transcription factors synthesized during training from the pre-existing mRNAs.
Assuntos
Amnésia Anterógrada , Vitis , Animais , Caracois Helix , Metilação de DNA , Amnésia/induzido quimicamente , Amnésia/metabolismo , Inibidores da Síntese de Proteínas/farmacologia , Transtornos da Memória/genética , Aprendizagem da EsquivaRESUMO
The participation of DNA methylation and histone acetylation in the mechanisms of anterograde amnesia and memory recovery was studied on grape snails trained in conditioned food aversion. Anterograde amnesia developed 10 days after memory reconsolidation impairment with an NMDA glutamate receptor antagonist and was characterized by long-term memory formation impairment upon repeated training. DNA methyltransferase inhibitor injections to snails 1 h before repeated training, as well as 15 min or 4 h after repeated training, caused rapid formation of memory that persisted for at least 10 days. Injections of histone deacetylase inhibitor before repeated training also induced the formation of a stable long-term memory. However, administration of histone deacetylase inhibitor 15 min after repeated training initiated a temporary memory recovery. Injections of the inhibitor 4 h after repeated training were ineffective. These results indicate that histone-dependent chromatin remodeling and DNA methylation are selectively involved in the mechanisms of anterograde amnesia and memory recovery.
Assuntos
Inibidores de Histona Desacetilases , Histonas , Inibidores de Histona Desacetilases/farmacologia , Metiltransferases , DNARESUMO
Impairment of reconsolidation of conditioned food aversion memory led to the development of a specific anterograde amnesia: repeated training of amnestic snails did not induce long-term memory formation. DNA demethylation caused by injections of DNA methyltransferase inhibitor (DNAMT) during repeated training led to long-term memory formation. Injections of an NMDA glutamate receptor antagonist or a serotonin receptor antagonist prevented memory formation induced by administration of DNAMT inhibitor and repeated training. We hypothesize that methylation-dependent repression of neuronal genes underlies anterograde amnesia. Demethylation eliminated the blockade of these genes and created conditions for long-term memory formation, the induction mechanisms of which involve neurotransmitter receptors.
Assuntos
Amnésia Anterógrada , Amnésia/induzido quimicamente , Amnésia/genética , Animais , Aprendizagem da Esquiva , Metilação de DNA , Caracois Helix/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de NeurotransmissoresRESUMO
Memory recovery in amnestic animals is one of the most poorly studied processes. In this paper, we examine the role of protein synthesis and a reminder in the mechanisms of amnesia and memory recovery in grape snails trained to conditioned food aversion. Amnesia was induced by the impairment of memory reconsolidation using NMDA (N-methyl d-aspartate) glutamate receptor antagonists. In an early stage of amnesia (day 3), injections of protein synthesis inhibitors into animals combined with a reminder by a conditioned stimulus (CS) led to the recovery of aversive reactions to its presentation. Two types of changes in reactions to CS were revealed. In most animals, a persistent recovery of memory retrieval was found that lasted for at least 10 days. In other snails, aversive responses to CS persisted for 24 h. Isolated injections of inhibitors, injections of inhibitors and a reminder by the learning environment (without presenting a CS), usage of a differentiating stimulus instead of a CS, or inhibitor injections after the reminder did not affect the development of amnesia. The administration of protein synthesis inhibitors and a reminder in the late period after amnesia induction (10 days) did not affect its development or caused a short-term memory recovery. We suggest that amnesia is an active process that develops over time. The reminder induces the reactivation of the amnesia process dependent on protein synthesis, while the administration of protein synthesis inhibitors leads to the impairment of amnesia reactivation and recovery of the state formed before amnesia induction (i.e., recovery of conditioned food aversion memory).
Assuntos
Amnésia/induzido quimicamente , Aprendizagem da Esquiva/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Consolidação da Memória/efeitos dos fármacos , Rememoração Mental/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , Animais , Condicionamento Operante/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Caracois Helix , Valina/análogos & derivados , Valina/farmacologiaRESUMO
The involvement of DNA methylation in the mechanisms of formation of conditioned food aversion memory was studied on Helix lucorum snails. The dynamics of aversion formation in snails injected with DNA methyltransferase inhibitor RG108 did not differ from that in control snails. The memory was retained for more than one month after training following RG108 injection and the duration of memory persistence did not differ from that in control animals. However, the characteristics of memory in control and experimental snails differed significantly. In control snails, injections of glutamate NMDA-receptor antagonist or protein synthesis inhibitor before memory retrieval caused disorders in the memory reconsolidation and development of amnesia 2 days after training. By contrast, injections of these substances before retrieval to snails trained against the background of RG108 treatment caused no memory disorders. We hypothesized that inhibition of DNA methylation processes led to the formation of strong memory, not reactivated after retrieval and not transformed into a labile state sensitive to amnesic agents.
Assuntos
Memória/fisiologia , Animais , Maleato de Dizocilpina/farmacologia , Memória/efeitos dos fármacos , Ftalimidas/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Triptofano/análogos & derivados , Triptofano/farmacologiaRESUMO
We studied the involvement of NMDA glutamate receptors in the mechanisms of anterograde amnesia. It was found that repeated training of amnestic animals treated with D-cycloserine, a potent agonist of the glycine site of NMDA receptors, did not lead to consolidation of long-term memory, while expression of short-term memory was more pronounced in comparison with control animals that received saline before repeated training. It was shown that D-cycloserine in amnestic snails did not affect the food reactions caused by the presentation of a conditioned stimulus during the reminder (without combination with the unconditioned stimulus). It is assumed that NMDA glutamate receptors in amnestic animals are involved in the neural plasticity mechanisms that underlie short-term memory, but their activation does not influence the anterograde amnesia processes and does not lead to the formation or recovery of long-term memory.
Assuntos
Amnésia Anterógrada/terapia , Ciclosserina/farmacologia , Ácido Glutâmico/metabolismo , Glicina/química , Caracois Helix/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Amnésia , Amnésia Anterógrada/fisiopatologia , Animais , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios , Memória , Memória de Longo Prazo , Memória de Curto Prazo , Modelos Animais , N-Metilaspartato , Plasticidade Neuronal , Receptores de Glutamato/metabolismo , Reprodutibilidade dos Testes , SinapsesRESUMO
The peculiarities of implication of NMDA glutamate receptors and protein synthesis into the mechanisms responsible for impairment of memory reconsolidation were studied in edible snails conditioned to food aversion. Injections of NMDA glutamate receptor antagonists or protein synthesis inhibitor prior to reminding with conditioned food stimulus provoked development of amnesia after different latent periods. NMDA glutamate receptor antagonists gradually weakened the aversive reactions to conditioned stimulus presented in parallel with reminder during 1 h. The protein synthesis inhibitor cycloheximide provoked the development of amnesia only 2.5 h after the onset of reminding procedure. Combined injections of protein synthesis inhibitor and NMDA glutamate receptor antagonist prior to reminding completely prevented the development of amnesia. The data agree with hypothesis that memory reconsolidation and amnesia are distinct processes, which need activation of synthesis of specific proteins.
Assuntos
Amnésia/induzido quimicamente , Receptores de N-Metil-D-Aspartato/agonistas , Animais , Cicloeximida/farmacologia , Caracois Helix , Memória/efeitos dos fármacosRESUMO
According to a common perspective, amnesia is a passive consequence of memory consolidation or reconsolidation impairment. The results of our own study, as well as literature data, allowed us to offer an interpretation of amnesia. Amnesia is an active process whose key characteristics are similar to those of other long-term plastic rearrangements of the brain, including learning processes. In accordance with this hypothesis, the review considers the data we obtained on the mechanisms of amnesia induction and development caused by impairment of conditioned food aversion memory consolidation or reconsolidation. In particular, experimental data indicating the dependence of amnesia induction on protein and RNA syntheses are described. After amnesia induction, a time-dependent reorganization of its processes is shown to occur. In early amnesia stages (< 10 days), a gradual decrease in the possibility of memory formation during a second training was observed. In late stages of amnesia (10 days or more), an unusual physiological phenomenon was revealed-the second training did not lead to the formation of long-term memory. This effect was specific, as memory for a new type of food could possibly be formed in these animals. The described properties of amnesia facilitate its characterization as specific anterograde amnesia. In addition, at an early but not late amnesia stages, reminder presentation caused amnesia reactivation, impairment of which by DNA methyltransferase inhibitors caused memory recovery. The results obtained allow us to characterize amnesia as a specific, time-dependent, separate process. In conclusion, the potential biological significance of the described type of amnesia is considered, and we discuss the possible molecular mechanisms underlying it.
Assuntos
Amnésia/metabolismo , Amnésia/fisiopatologia , Aprendizagem da Esquiva/fisiologia , Consolidação da Memória/fisiologia , Memória de Longo Prazo/fisiologia , Prática Psicológica , AnimaisRESUMO
We studied the involvement of protein kinase Mζ (PKMζ) in the mechanisms of amnesia development within 10 days after disruption of conditioned food aversion memory with ZIP (a PKMζ inhibitor). Repeated training performed in 3 days after amnesia induction with ZIP, led to the formation of conditioned food aversion memory, but the number of combined presentations of food and reinforcer stimuli was lower than during the initial training. Repeated training performed in 10 days after amnesia induction also led to memory formation, but the number of combined presentations of the stimuli was similar to that during the initial training. It was hypothesized that at the early stages of ZIP-induced amnesia, residual memory trace can be restored and amplified during repeated training, which led to memory expression at the behavioral level. At the late stages of amnesia, this memory trace was completely erased and repeated training led to the formation of a new memory. Thus, PKMζ inhibition results in the relatively fast impairment of memory retrieval and induces long-term process of memory erasing.
Assuntos
Amnésia/induzido quimicamente , Lipopeptídeos/farmacologia , Memória de Longo Prazo/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Amnésia/psicologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Peptídeos Penetradores de Células , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Condicionamento Psicológico/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Caracois Helix/efeitos dos fármacos , Caracois Helix/fisiologia , Consolidação da Memória/efeitos dos fármacos , Consolidação da Memória/fisiologia , Proteína Quinase C/antagonistas & inibidores , Fatores de TempoRESUMO
Administration of 5-HT receptor antagonist to snails trained in conditioned food aversion prior to reminding of the conditioning stimulus caused amnesia. At the early period of amnesia (day 3), injections of protein synthesis inhibitor cycloheximide without reminder or reminder alone were ineffective. At the same time, injections of the inhibitor combined with reminder led to memory recovery; this effect in most animals persisted for at least 10 days. In the rest snails, aversive responses to presentations of the conditioning stimulus persisted for 2 days. Cycloheximide injection and reminder in 10 days after induction of amnesia did not affect its development or caused a transient memory recovery (2 days). We hypothesized that amnesia is an active process unfolding in time. One of mechanism of this process is reminder-induced and protein synthesis-depended reactivation of amnesia. Inhibitor of protein synthesis disturbed this reactivation and led to recovery of the initial memory of conditioned food aversion.
Assuntos
Amnésia/tratamento farmacológico , Amnésia/etiologia , Cicloeximida/uso terapêutico , Transtornos da Memória/induzido quimicamente , Memória/efeitos dos fármacos , Metiotepina/farmacologia , Inibidores da Síntese de Proteínas/uso terapêutico , Antagonistas da Serotonina/farmacologia , Animais , CaramujosRESUMO
The involvement of protein synthesis in the mechanisms of conditioned food aversion memory impairment and recovery in grape snails was studied. It was found that protein synthesis inhibitor (cycloheximide) injections before a reminder by the conditioned stimulus (CS) caused amnesia development. Three days after amnesia induction, injections of cycloheximide or another protein synthesis inhibitor, anisomycin, combined with a reminder by four CSs resulted in memory retrieval, which was saved for 24 h. Cycloheximide injections and the administration of one CS as a reminder to an amnestic animals caused the memory expression only in response to this CS, while it was absent the next day. The isolated administration of a reminder or inhibitor injections without a reminder was not effective. It is suggested that amnesia is an active process and that one of its mechanisms may be a protein-dependent amnesia reactivation caused by a reminder. The administration of protein synthesis inhibitors led to impairment of amnesia reactivation and to recovery of the state formed before amnesia induction and thus to the recovery of conditioned food aversion memory.
Assuntos
Anisomicina/toxicidade , Cicloeximida/toxicidade , Transtornos da Memória/induzido quimicamente , Inibidores da Síntese de Proteínas/toxicidade , Recuperação de Função Fisiológica/efeitos dos fármacos , Animais , Condicionamento Clássico/efeitos dos fármacos , Modelos Animais de Doenças , Esquema de Medicação , Estimulação Elétrica/efeitos adversos , Alimentos , Transdução de Sinais/efeitos dos fármacos , Caramujos , Estatísticas não Paramétricas , Fatores de TempoRESUMO
We studied the participation of DNA-methylation processes in the mechanisms of memory storage and reconsolidation, amnesia induction, and in recovery of the conditioned food aversion memory in edible snails. It was found that daily injections of DNA methyltransferases inhibitor over 3 days combined with a reminder of a conditioned food stimulus did not affect memory storage. The administration of DNA methyltransferase inhibitors did not suppress induction of amnesia caused the NMDA receptor antagonist/reminder. Injections of DNA methyltransferase inhibitors combined with the reminder led to memory recovery in 3 days after amnesia induction. Thus, DNA methyltransferase inhibitors in the same doses did not affect storage and reconsolidation of memory, as well as the mechanisms of amnesia induction. At the same time, injections of inhibitors led to memory recovery, apparently, due to disruption of reactivation and amnesia development.
Assuntos
Metilases de Modificação do DNA/metabolismo , Memória/efeitos dos fármacos , Ftalimidas/farmacologia , Triptofano/análogos & derivados , Valina/análogos & derivados , Amnésia/tratamento farmacológico , Amnésia/enzimologia , Amnésia/prevenção & controle , Animais , Metilases de Modificação do DNA/antagonistas & inibidores , Caracois Helix , Ftalimidas/uso terapêutico , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Triptofano/farmacologia , Triptofano/uso terapêutico , Valina/farmacologia , Valina/uso terapêuticoRESUMO
Elucidation of amnesia mechanisms is one of the central problems in neuroscience with immense practical application. Previously, we found that conditioned food presentation combined with injection of a neurotransmitter receptor antagonist or protein synthesis inhibitor led to amnesia induction. In the present study, we investigated the time course and features of two amnesias: induced by impairment of memory reconsolidation using an NMDA glutamate receptor antagonist (MK-801) and a serotonin receptor antagonist (methiothepin, MET) on snails trained with food aversion conditioning. During the early period of amnesia (<10th day), the unpaired presentation of conditioned stimuli (CS) or unconditioned stimuli (US) in the same training context did not have an effect on both types of amnesia. Retraining an on 1st or 3rd day of amnesia induction facilitated memory formation, i.e. the number of CSâ¯+â¯US pairings was lower than at initial training. On the 10th or 30th day after the MET/reminder, the number of CSâ¯+â¯US pairings did not change between initial training and retraining. Retraining on the 10th or 30th day following the MK-801/reminder in the same or a new context of learning resulted in short, but not long-term, memory, and the number of CSâ¯+â¯US pairings was higher than at the initial training. This type of amnesia was specific to the CS we used at initial training, since long-term memory for another kind of CS could be formed in the same snails. The attained results suggest that disruption of memory reconsolidation using antagonists of serotonin or NMDA glutamate receptors induced amnesias with different abilities to form long-term memory during the late period of development.
Assuntos
Amnésia/induzido quimicamente , Antagonistas de Aminoácidos Excitatórios/farmacologia , Memória/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Antagonistas da Serotonina/farmacologia , Amnésia/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Maleato de Dizocilpina/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Comportamento Alimentar/psicologia , Caracois Helix , Memória/fisiologia , Metiotepina/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Fatores de TempoRESUMO
Mechanisms of amnesia caused by impairment of consolidation or reconsolidation of conditioned food aversion memory with protein synthesis inhibitor cycloheximide were studied in Helix lucorum. Cycloheximide injection during training or memory reconsolidation in trained snails produced amnesia. In both cases, repeated training 10 days after amnesia induction led to short-term memory formation, while long-term memory was not formed, despite the fact that the number of conditioned and reinforcing stimuli combinations was higher than during initial training. The possibility of formation of short-term memory not transforming into long-term memory is one of the key characteristics of anterograde amnesia. Our findings data and experimental model can be used for analysis of specific molecular mechanisms of anterograde amnesia.
Assuntos
Amnésia Anterógrada/induzido quimicamente , Consolidação da Memória , Animais , Aprendizagem da Esquiva , Cicloeximida , Comportamento Alimentar , Caracois HelixRESUMO
Experiments were performed on the snails trained in conditioned food aversion for 3 days. Injection of TDZD-8 (glycogen synthase kinase-3 inhibitor, 2 mg/kg) in combination with reminder (presentation of a conditioned food stimulus) led to memory impairment developing 3 days after inhibitor/reminder exposure and followed by spontaneous recovery in 10 days. Injections of TDZD-8 in a dose of 4 or 20 mg/kg before reminder were shown to cause amnesia that persisted for more than 10 days. Memory recovery during repeated training was observed at the earlier period than after initial training. The impairment of memory reconsolidation by TDZD-8 after training of snails for 1 day was less pronounced than under standard training conditions (3 days). The effect of a glycogen synthase kinase-3 inhibitor during memory reconsolidation is probably followed by impairment of memory retrieval and/or partial loss, which can be compensated spontaneously or after repeated training.
Assuntos
Amnésia/enzimologia , Condicionamento Clássico/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Caracois Helix/efeitos dos fármacos , Consolidação da Memória/efeitos dos fármacos , Tiadiazóis/farmacologia , Amnésia/induzido quimicamente , Amnésia/genética , Amnésia/fisiopatologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/fisiologia , Relação Dose-Resposta a Droga , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Regulação da Expressão Gênica , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Caracois Helix/fisiologia , Consolidação da Memória/fisiologia , Memória de Longo Prazo/efeitos dos fármacos , Memória de Longo Prazo/fisiologia , Fatores de TempoRESUMO
Specificity of behavioral and neuronal mechanisms of impairment of long-term memory reconsolidation was studied in edible snails trained for associative skill of rejection of two types of food: raw carrots (conditioned stimulus 1) and apple (conditioned stimulus 2). In 2 days after training, the snails received protein synthesis inhibitor cycloheximide and a reminder (conditioned stimulus 1 or 2). In 3 and 14 days after cycloheximide/reminder, we observed the absence of aversive responses to the conditioned stimulus used as the reminder and preserved responses to the conditioned stimulus not used as the reminder. Moreover, we observed specific suppression of synaptic responses of command neurons of snail defensive behavior induced by the conditioned stimulus used as the reminder after cycloheximide injection and preserved synaptic responses of neurons to the other conditioned stimulus. It was hypothesized that protein synthesis-dependent synapse-specific plasticity of command neurons can be a mechanism of selective preservation of conditioned food aversion memory in snails.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Caracois Helix/fisiologia , Consolidação da Memória/efeitos dos fármacos , Memória de Longo Prazo/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Cicloeximida/farmacologia , Daucus carota , Comportamento Alimentar/fisiologia , Caracois Helix/efeitos dos fármacos , Malus , Consolidação da Memória/fisiologia , Memória de Longo Prazo/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Inibidores da Síntese de Proteínas/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologiaRESUMO
The dynamics of amnesia development under conditions of memory reconsolidation disruption by serotonin receptor antagonist methiothepin or NMDA glutamate receptor antagonist MK-801 was studied in snails trained in conventional food aversion. In 2 days after training, injection of methiothepin or MK-801 before reminder induced amnesia development. During repeated training in 3 days after amnesia induction, the skill was formed more rapidly than during the initial training. During repeated training in 10 days after administration of methiothepin and reminder, the dynamics of habit formation was similar to that during initial learning. At the same time, repeated training in 10 days after MK-801 administration and reminder did not result in long-term memory formation. Disruption of reconsolidation of conditioned food aversion memory by antagonists of serotonin or NMDA glutamate receptors led to the development of different types of amnesia that had similar strengthening gradient at the early stages, but differed by the possibility of memory formation during re-training at the late stage.
Assuntos
Amnésia/induzido quimicamente , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Caracois Helix/efeitos dos fármacos , Memória de Longo Prazo/efeitos dos fármacos , Metiotepina/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de Neurotransmissores/antagonistas & inibidores , Antagonistas da Serotonina/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacosRESUMO
We studied the role of glutamate receptors and reminder in the mechanisms of amnesia maintenance caused by disruption of conditioned food aversion reconsolidation with an antagonist of NMDA glutamate receptor in snails. At the early stage of amnesia (day 3 after induction), injection or NMDA of AMPA glutamate receptor antagonists prior to reminder (presentation of the conditioned food stimulus) led to memory recovery. Reminder alone or injection of antagonists without reminder or after reminder was ineffective. At the late stage of amnesia (day 10), antagonists/reminder had no effect on amnesia maintenance. It was hypothesized that reminder at the early stage of amnesia led to reactivation and reconsolidation of the molecular processes of amnesia including activation NMDA and AMPA glutamate receptors. Injection of antagonists of these receptors prior to reminder led to disruption of reactivation/reconsolidation of amnesia and recovery of the conditioned food aversion memory.
Assuntos
Amnésia/fisiopatologia , Aprendizagem da Esquiva/fisiologia , Caracois Helix/fisiologia , Consolidação da Memória/fisiologia , Receptores de AMPA/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Eletrochoque , Antagonistas de Aminoácidos Excitatórios/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Consolidação da Memória/efeitos dos fármacos , Quinoxalinas/farmacologia , Fatores de TempoRESUMO
We studied the involvement of Mζ-like protein kinase (PKMζ) into mechanisms of conditioned food aversion memory reconsolidation in Helix lucorum. Injections PKMζ inhibitor ZIP in a dose of 5 mg/kg on day 2 or 10 after learning led to memory impairment and amnesia development. Injections of the inhibitor in doses of 1.5 or 2.5 mg/kg had no effect. Repeated training on day 11 after induction of amnesia resulted in the formation of memory on the same type of food aversion similar to first training. The number of combinations of conditional (food) and reinforcing (electrical shock) stimuli was similar during initial and repeated training. We hypothesize that the inhibition of Mζ-like protein kinase erases the memory trace and a new memory is formed during repeated training.