INFLUENCE OF ETHANOL WITHDRAWAL ON FEAR MEMORY: EFFECT OF d-CYCLOSERINE

BERTOTTO ME, BUSTOS SG, MOLINA VA, MARTIJENA ID

NEUROSCIENCE

Elsevier

Año: 2006 vol. 142 p. 979 - 990

0306-4522

Abstract  Animals made dependent via an ethanol-containing liquid diet (6% v/v) for 14 days were submitted to a contextual fear conditioning paradigm 3 days after the last consumption day. After conditioning, rats were subjected to 4 extinction trials by exposing the animals to the conditioned context and their freezing was evaluated for each trial. Immediately after the first extinction trial, all animals were either injected with saline or D-cycloserine 5 mg/kg i.p - a dose that did not influence the extinction in control rats -. Spontaneous recovery of learned fear was tested seven days after the last extinction trial. The following day, animals were submitted to a reacquisition or a reinstatement procedure and their freezing responses evaluated 24 h later. The present study shows that: 1. discontinuation from chronic ethanol administration facilitated the formation of a new fear memory concomitant with a marked resistance to being extinguished, 2. administration of D-cycloserine (5 mg/kg) facilitated the extinction process only in withdrawn rats, 3. both reinstatement and reacquisition procedures restored the increased freezing in withdrawn animals after extinction, 4. DCS administered immediately after the first extinction trial prevented the increase in freezing following both reacquisition and reinstatement. The enhanced sensitivity to the facilitatory effect of DCS in ethanol withdrawn animals may be mediated by adaptive changes in NMDA receptor provoked by ethanol dependence.