Positive emotional induction interferes with the reconsolidation of negative autobiographical memories, in women only.

After reactivation, a previously consolidated memory can enter into a labile state followed by a re-stabilization process defined as reconsolidation. The aim of this study was to explore whether an existing negative autobiographical memory can be modified by using a non-invasive interference (audiovisual positive preparation) after reactivation and to determine if this effect could be dependent on the reconsolidation process. We found that the presentation of a positive inductor after a negative autobiographical memory reactivation may lead to a change in the emotional information of the original trace and that such effect can be mediated by the reconsolidation process. The modification of the memory has been shown in women only. These results suggest that a positive audiovisual induction may play a potential role in psychotherapeutic techniques for the modification of dysfunctional autobiographical memories.

Influence of ethanol withdrawal on fear memory: Effect of D-cycloserine.

Animals made dependent via an ethanol (ETOH) -containing liquid diet (6% v/v) for 14 days were subjected to a contextual fear conditioning paradigm 3 days after the last consumption day. After conditioning, rats were subjected to four extinction trials by exposing the animals to the conditioned context and their freezing was evaluated for each trial. Immediately after the first extinction trial, animals were injected with D-cycloserine (DCS) 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 subjected to a reacquisition or a reinstatement procedure and their freezing responses evaluated 24 h later. The present study shows that: 1. discontinuation from chronic ETOH administration facilitated the formation of a new fear memory concomitant with a marked resistance to being extinguished, 2. administration of DCS (5 mg/kg) facilitated the extinction process only in ETOH withdrawn rats, 3. both reinstatement and reacquisition procedures restored the increased freezing in ETOH withdrawn animals after extinction, 4.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 ETOH withdrawn animals may be mediated by adaptive changes in N-methyl-D-aspartate (NMDA) receptor provoked by ETOH dependence.

Midazolam disrupts fear memory reconsolidation.

The current research examines the influence of midazolam (MDZ) on memory reconsolidation using a contextual fear paradigm in rats, based on three context-shock training trials (0.7 mA, 3 s). First, we evaluate the effect of MDZ (1 mg/kg, i.p.) injected shortly after the training procedure. Second, we examined the influence of MDZ after a brief exposure (90 s) either in the training context (reactivation procedure) or in a neutral environment (no reactivation procedure) and one day later, freezing behavior was scored when rats were re-exposed to the training environment. Third, we investigate both the effect of MDZ administered at different times following reactivation on fear memory and the persistence of such effect 10 days after reactivation. Finally, we test whether the MDZ effect could be reverted by a single weak training trial (0.2 mA, 3 s) or by the presentation of the same unconditioned stimulus in the absence of the conditioned stimulus as a reminder which proves to induce significant freezing in rats not previously trained. Results show that MDZ interferes with the formation of a contextual fear memory only when administered after the reactivation procedure but not after the training procedure. This interference was effective up to 60 min after reactivation and not at a later time. No spontaneous recovery of freezing behavior was observed 11 days after MDZ injection which was not reverted by a weak training trial and by the unconditioned stimulus alone. All these data support the idea that stimulating GABA A receptor sites via MDZ selectively disrupts the reconsolidation process of a contextual fear memory.

Chronic benzodiazepine administration facilitates the subsequent development of ethanol dependence.

This study investigated the effect of chronic benzodiazepine (BZD) administration and its abrupt discontinuation on later subsequent ethanol consumption employing a free choice paradigm between water and increasing ethanol concentrations. In addition, we also studied the anxiolytic and reinforcing properties of ethanol assessed in the elevated plus maze (EPM) and in the conditioned place preference paradigm, respectively. Adult male Wistar rats were subjected to a chronic diazepam (DZM) treatment (2 mg/kg/day, i.p.) during 21 days. Twenty-four hours after that treatment and, in another experiment, 10 days after the last DZM injection, rats were subjected to an oral ethanol self-administration procedure (ethanol was increased in concentration (v/v) on 4 consecutive days as follows: 2%, 4%, 6%, 8% followed by an additional period of 8 days in which animals were offered a 10% (v/v) ethanol solution. Diazepam treated rats showed a higher ethanol intake and spontaneous signs of ethanol withdrawal when the access to ethanol was discontinued. These results were observed when ethanol was available at day 1 of withdrawal but not when DZM treated rats were initiated in the ethanol choice test 10 days after BDZ withdrawal. Furthermore, DZM treated rats exhibited an increased anxiolytic ethanol induced effect (1 g/kg, i.p.) in the EPM and a significant ethanol-induced conditioned place preference (1 g/kg, i.p.). These data suggest that early DZM treatment facilitates ethanol consumption and the development of ethanol dependence.

Benzodiazepine withdrawal facilitates the subsequent onset of escape failures and anhedonia: influence of different antidepressant drugs.

The effect of benzodiazepine (BDZ) withdrawal on escape acquisition and on the behavioral response to two different reinforcing stimuli was investigated. In addition, the influence of antidepressant drugs (AD) differing in their mechanism of action on these behavioral outputs was also evaluated. Rats subjected to withdrawal from a chronic treatment with diazepam (DZM; 2 mg/kg per day, i.p.) during 21 days were subsequently exposed to a brief inescapable shock session (IS) and 48 h later to an active avoidance test. Only withdrawn animals exposed to the IS exhibited enhanced escape failures. In an additional experiment, withdrawn rats were repeatedly administered with vehicle (VEH), desipramine (DMI; 5 mg/kg, i.p.), fluoxetine (FLU; 5 mg/kg, i.p.) or phenelzine (PHEN; 5 mg/kg, i.p.) and subsequently exposed to IS and to active avoidance task. A significant reversal of escape deficit was only observed following DMI and PHEN but not after FLU. Furthermore, withdrawn rats showed a reduced preference for a sexually relevant olfactory cue, this reduced sensitivity was only normalized following DMI but not after the administration of FLU or PHEN. Finally, rats exposed to abrupt cessation of chronic BDZ administration did not exhibit preference for a context previously associated with amphetamine (AMP) under the conditioned place preference (CPP) procedure. All these findings are indicative that BDZ withdrawal facilitates the subsequent occurrence of behavioral changes-escape failures and reduced behavioral response to rewarding stimuli-suggested to parallel important symptoms of human depression. In addition, DMI seems to be much more effective in restoring such behavioral abnormalities as compared to a MAO inhibitor and to a inhibitor of 5-HT uptake.