Dados do Trabalho

Título

PERIODICAL REACTIVATION UNDER THE EFFECT OF CAFFEINE ATTENUATES FEAR MEMORY EXPRESSION IN RATS

Introdução

Exposure to highly aversive experiences can lead to the formation of enduring traumatic memories, which can trigger debilitating psychiatric disorders such as posttraumatic stress disorder and phobias. Therapeutic strategies that target memory reconsolidation may attenuate persistent fear memories. These involve the transient labilization of the memory trace induced by a reactivation session that makes the original memory susceptible to pharmacological and behavioral modifications. Except for some drugs, like propranolol and ketamine, most reconsolidation inhibitors are not approved for human testing. Caffeine, a non-selective antagonist of adenosine receptors, is a popular psychoactive drug that may bring a new pharmacological approach to treat fear-related disorders.

Objetivo

To assess the effect of caffeine on the attenuation of a strong contextual fear memory expression in rats, using a reconsolidation protocol.

Método

Adult male and female rats were trained using a contextual fear conditioning protocol and received caffeine or vehicle before each reactivation session (days 7, 13 and 19) and tested in a drug-free condition on day 25. Freezing, an innate defensive behavior, was used as a memory retention index. Repeated-measures ANOVA was used to compare vehicle and caffeine groups and statistical significance was set at p<0.05.

Resultados

In males, Repeated-measures ANOVA revealed significant effects of treatment factor (vehicle vs. caffeine) (F1,10=21.579; p<0.001) and time factor (reactivation vs. test) (F3,30=8.343; p<0.001) but not for treatment x time interaction (F3,30=0.554; p=0.649). Post-hoc analysis showed that with the exception of reactivation 1 (p=0.082), caffeine-treated rats expressed less freezing in the remaining reactivation sessions (2 and 3) (p<0.05) and during the test session (p<0.05). In females, Repeated-measures ANOVA revealed significant effects of treatment factor (vehicle vs. caffeine) (F1,15=19.691; p<0.001), time factor (reactivation vs. test) (F3,45=22.472; p<0.001), and treatment x time interaction (F3,45=5.756; p=0.002). Post-hoc analysis showed that caffeine-treated rats expressed less freezing compared to controls (p<0.01) in reactivation sessions 1 and 2. However, these differences were not detected during reactivation 3 and in the test session (p>0.05). Moreover, there was a significant difference within group in control animals in all reactivation and test sessions (p<0.05), suggesting an accelerated extinction process.

Conclusão

These results suggest strong fear memory can be weakened using a widely used drug during memory reactivation.

Palavras-chave

Reconsolidation
Caffeine
Rat