Adults male Wistar rats treated with an ethanol-containing liquid diet (6% v/v) for 14 days were submitted to a fear conditioning paradigm (3 footshocks, 0.4mA, 3s, ITI: 30s) 3 days after the last consumption. Rats were then subjected to 4 extinction trials performed 24, 48, 72 and 96 h later by exposing the animals to the conditioned context and freezing was registered during each trial for 10 min. Immediately after the first extinction trial, half of the animals were injected with d-cycloserine (DCS, 5 mg/kg i.p- a dose that does not influence the extinction in control rats) and the other half with saline. The spontaneous recovery of learned fear was tested seven days after the last extinction trial. The next day, animals were submitted to a reacquisition (1 footshock, 0.4mA, 3s, in the conditioned context) or reinstatement (1 footshock, 0.4mA, 3s, in a new context) procedure and the freezing response was evaluated in the respective context 24 h later.
A comparable low level of fear behavior was detected in all animals 7 days after the last extinction trial indicating retention of extinction memory. Following reinstatement or reacquisition training ethanol withdrawn animals displayed higher levels of freezing than controls and this increase was prevented by DCS pretreatment. The enhanced sensitivity to the facilitatory effect of DCS in ethanol withdrawn animals may be mediated by adaptive changes in NMDA receptor induced by ethanol dependence.
