Effect of extinction and withdrawal on NR2B

The current studies showed that antagonism of NR2B-containing NMDARs by
ifenprodil effectively disrupted the acquisition and reconsolidation of Fix-C and Esc-C
memory. However, ifenprodil had no effect on stress-induced reinstatement of Fix-C and
Esc-C CPP. One possible explanation for this lack of effect is that NR2B subunit may
have been replaced by NR2A during the time of extinction and withdrawal from cocaine.
Thus, with reduced expression of NR2B at the time of reinstatement, a selective NR2B
antagonist would have no effect on the behavior. My findings are in accordance with
others who found that NR2B-containing NMDARs are required for morphine-induced
reinstatement but not forced swim-induced reinstatement of morphine CPP (Ma et al.,
2006). This suggests that at the time of reinstatement, exposure to the drug (such as
morphine or cocaine) engages NR2B-containing NMDARs to reinstate place preference.
However, it appears that exposure to stress induces reinstatement in a manner
independent of NR2B-containing NMDARs. Thus, future studies should investigate a)
how levels of NR2B change with extinction and withdrawal and b) other possible
signaling molecules/pathways that interact with stress-related molecules to induce
reinstatement of extinguished place preference.


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