ETHANOL WITHDRAWAL AFFECTS THE MECHANISM OF FEAR MEMORY LABILIZATION IN THE BASOLATERAL AMYGDALA COMPLEX: EFFECT OF D-CYCLOSERINE

París

Congreso; International Society of Neurochemistry (ISN) and the European Society for Neurochemistry (ESN); 2017

Contextual fear memory formed under withdrawal from chronic ethanol consumption is resistant to pharmacological interference with the reconsolidation process; indicating a resistance to the occurrence of the labilization phase after recall. In addition, pre-retrieval D-cycloserine (DCS) administration facilitates the reconsolidation interference of this resistant memory. The molecular mechanisms underlying the influence of ethanol withdrawal or DCS on fear memory labilization have not been established yet. Thus, here we evaluated the ubiquitin-proteasome system (UPS) activity in the basolateral amygdala complex (BLA) after fear memory retrieval in ethanol withdrawn (ETOH) animals, and the influence of DCS on this molecular pathway. For this, we examined the polyubiquitinated proteins levels by Western Blot and proteasome chymotrypsin-like activity by enzymatic assay. Male Wistar rats were made dependent via an ethanol containing liquid diet (6% v/v) for 14 days. The respective control (CON) group was pair-fed with the same diet without ethanol. Contextual fear conditioning was performed on day 3 of withdrawal. Seven days after, rats were subjected or not to memory retrieval and were sacrificed 60 min later. In addition, separated CON and ETOH animals received DCS (5 mg/kg, i.p) or saline (SAL) injection 30 min before retrieval and were sacrificed 60 min later. Our results indicated that the retrieval only induced an increase in polyubiquitinated proteins expression and proteasome activity in the BLA from CON rats, whereas those effects were not observed in ETOH rats. These animals showed UPS activity patterns similar to those of the groups not subjected to retrieval. In the second experiment, we observed that ETOH rats treated with DCS before retrieval displayed elevated and similar UPS activity to CON rats after recall. In summary, ethanol withdrawal affects the neurobiological mechanisms involved in the fear memory labilization and DCS favors this molecular pathway in ethanol ETOH rats.