d-cycloserine in the basolateral amygdala prevents extinction and enhances reconsolidation of odor-reward associative learning in rats

Abstract

It is well established that D-cycloserine (DCS), a partial agonist of the NMDA receptor glycine site, enhances learning and memory processes. Although the effects of DCS have been especially elucidated in the extinction and reconsolidation of aversive behavioral paradigms or drug-related behaviors, they have not been clearly determined in appetitive tasks using natural reinforcers. The current study examined the effects of pre-retrieval intra-basolateral amygdala (BLA) infusions of DCS on the extinction and reconsolidation of an appetitive odor discrimination task. Rats were trained to discriminate between three odors, one of which was associated with a palatable food reward and, twenty minutes prior to extinction learning (experiment 1) or reactivation (experiment 2), they received bilateral intra-BLA infusions of DCS or vehicle. In experiment 1, DCS infusion reduced the rate of extinction learning acquisition, weakened extinction retention in a post-extinction test and enhanced reacquisition of the ODT task. In experiment 2, DCS improved subsequent memory expression in the reconsolidation test performed one day after the reactivation session. Such results indicate the involvement of BLA NMDA receptors in odor-food reward associative memory and suggest that DCS may potentiate the persistence or strength of the original memory trace.

D-cycloserine in Prelimbic Cortex Reverses Scopolamine-Induced Deficits in Olfactory Memory in Rats

“…In this regard, there is evidence showing, on the one hand, that DCS facilitated ODT [15], conditioned fear responses [64], [65], [66], conditioned flavor-taste preference and conditioned-taste aversion [13], [67], or procedural learning in humans [68]. On the other hand, no facilitative effects of DCS administration were found in the retention of Morris water maze (MWM) learning in rodents [69], [70], or declarative word-pair learning in humans [68].…”

“…The DCS dosage, for example, may not have been optimal, which is an important factor in that the therapeutic window for DCS to enhance human fear memory extinction has been reported as narrow [78]. In this respect, although the previous studies testing intracerebral DCS administration used the same dosage (10 µg/site) [15], [31], [79], [80], [81], higher doses might have been more appropriate to find enhancing effects in VEH rats. Indeed, it has been reported that only a higher dose of systemic DCS was able to promote episodic-like memory [61], although lower doses potentiated memory in non-relational aversive paradigms [82].…”

“…Specifically, injections in the medial septum or CA1 [9] or the ventral tegmental area [10] induced amnesia in inhibitory avoidance. Secondly, systemic pre-learning infusions of d-cycloserine (DCS), a NMDAR partial agonist at the glycine modulatory site that enhances memory processes [11], [12], [13], [14], [15], attenuated SCOP-induced deficits in the acquisition of spatial tasks [16], [17], [18], [19]. Additionally, it has been shown that acute application of memantine also reversed SCOP-induced learning impairments in the water maze [3].…”

Stress-induced resistance to the fear memory labilization/reconsolidation process. Involvement of the basolateral amygdala complex

“…The total volume of drug used was 1.0ml/kg, or an equivalent amount of SAL, in all cases. For intra-BLA infusion, DCS was dissolved in SAL to a final concentration of 40 µg/µl and the amount infused was 10 µg/side (Lee et al, 2009;Portero-Tresserra et al, 2013).…”

Hippocampal activation during extinction learning predicts occurrence of the renewal effect in extinction recall

“…The amygdala appears to be necessary for processes that involve updating of representations of value, not only in fear extinction, but also in reinforcer devaluation (Morrison and Salzman, 2010). Accordingly, amygdala participation in appetitive extinction has been demonstrated for food-reward extinction learning (Judice-Daher et al, 2012;Portero-Tresserra et al, 2013), for extinction of responding to a visual CS which had been paired with food reward (Lindgren et al, 2003). Recent neuroimaging studies suggest that the human amygdala is involved in many reward-based decision-making tasks (Morrison and Salzman, 2010).…”