RESUMO
Two experiments using rats in a contextual fear memory preparation compared two approaches to reduce conditioned fear: (1) pharmacological reconsolidation blockade and (2) reactivation-plus-extinction training. In Experiment 1, we explored different combinations of reactivation-plus-extinction parameters to reduce conditioned fear and attenuate reacquisition. In Experiment 2, memory reactivation was followed by extinction training or administration of midazolam (MDZ) (vs. vehicle) to reduce conditioned fear and attenuate spontaneous recovery. We found both treatments to be equally effective in both experiments. This study suggests that parameters leading to memory destabilization during reactivation are critical to observe long-lasting effects of MDZ or reactivation plus extinction.
Assuntos
Medo/efeitos dos fármacos , Medo/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Testes Psicológicos , Animais , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Masculino , Midazolam/farmacologia , Psicotrópicos/farmacologia , Distribuição Aleatória , Ratos WistarRESUMO
Three experiments using rats in an appetitive conditioning procedure analyzed the effect of short and long (50s vs. 1440s) intertrial intervals (ITI) over the acquisition of conditioned stimulus (CS), context (Ctxt), and unconditioned stimulus (US) associations, as well as the effect on the extinction and renewal of the conditioned response to the CS. Experiment 1 revealed more contextual conditioned responses in groups trained with the short ITIs, however the renewal effect was not observed during test phase with either ITI condition. When subjects were pre-exposed to the contexts before the acquisition phase (Experiment 2) renewal of the conditioned response (CR) was only observed in long ITI group. However, when the acquisition context was extinguished (Experiment 3) the renewal effect observed in the Experiment 2 was weakened. In all three experiments subjects showed a similar number of responses to the tone predicting food, however they showed a clear contextual conditioning effect only for the groups trained with short ITIs. It is noteworthy that the acquisition context showed high levels of the CR in the renewal test only for groups trained with short ITIs (Experiment 2) but these responses were absent if additional contextual extinction was imposed before such test (Experiment 3). In general, all groups showed similar acquisition curves for the CS but only Short groups had an increase in the CR during the pre-CS. Also, context conditioning does not interfere with the conditioning of the CS and context pre-exposure prior to acquisition is essential in order to observe the renewal effect when long ITIs are used.
Assuntos
Comportamento Animal/fisiologia , Condicionamento Clássico/fisiologia , Aprendizagem/fisiologia , Ratos/fisiologia , Animais , Comportamento Apetitivo/fisiologia , Feminino , Masculino , Ratos Wistar , Fatores de TempoRESUMO
It has been suggested that, unlike pure extinction which typically results in the return of the fear response under a variety of circumstances, memory reactivation followed by extinction can attenuate the reemergence of conditioned fear. The reactivation-extinction procedure has attracted the attention of basic and clinical researchers due to its potential clinical value for the treatment of psychiatric conditions, such as anxiety and drug abuse disorders. However, mixed results have been achieved so far in replicating and understanding this paradigm. It has been proposed that memory destabilization could be critical in this sense. Using contextual fear conditioning in rats and midazolam as an amnesic agent, we first determined what reactivation conditions are necessary to destabilize the mnemonic trace. After establishing the conditions for memory destabilization, a series of experiments was conducted to determine if destabilization is critical for the success of the reactivation-extinction procedure. Data confirmed the importance of memory destabilization prior to extinction inside the reconsolidation window to attenuate spontaneous recovery and retard reacquisition of conditioned fear. The present report offers a candidate explanation of the discrepancy in results obtained with the reactivation-extinction procedure by different laboratories.