Maladaptive behaviors such as anxiety disorders are associated with learning and memory processes. Fear conditioning is often used as a model for understanding anxiety disorders including post-traumatic stress disorder (PTSD). Like CPP experiments, fear conditioning is based on Pavlovian conditioning in which an organism learns to…

While the current studies identified that the NMDAR and NO-signaling play a role in stress-induced reinstatement of Fix-C CPP, an effective test drug against Esc-C memory was not identified. Since Esc-C memory represents a ‘stronger’ and more ‘resistant’ type of drug memory compared to Fix-C memory,…

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…

The current studies employed systemically administered modulators of various signaling molecules and showed in some instances a similar effect on Fix-C and Esc-C memory while in other cases differential effects. While the use of pharmacological tools could be the gold standard for the treatment of human…

Recent reports demonstrate that repeated cocaine exposure generate silent glutamatergic synapses which contribute to metaplasticity (Huang et al, 2009) and the development of cocaine-induced locomotor sensitization (Brown et al, 2011). Silent synapses are glutamatergic synapses which express NMDAR-mediated currents in the absence of AMPAR-mediated currents (Isaac…

My findings opened up several avenues for additional research. First, an investigation of the role of silent synapses (see below) in cocaine-associated memory strength will help to identify a mechanism through which NR2B-containing NMDARs contribute to Fix-C and Esc-C memory. Second, site-specific inhibition of signaling targets…

Vulnerability to relapse following prolonged periods of abstinence presents a major challenge to combating drug addiction. Stress is an unavoidable part of life and a major contributor to relapse to drug use. However, a thorough understanding of the neural mechanisms that sub-serve stress-mediated relapse is lacking.…

Increasing lines of evidence suggest that retrieval of previously consolidated memories is a dynamic process that either reinforces or alters memory. Memory retrieval may initiate two potentially opposing but distinguishable processes: reconsolidation and extinction (Suzuki et al., 2004). Memory reconsolidation acts to stabilize retrieved memories whereas…

The CPP paradigm which employs the principles of Pavlovian learning is often used to investigate the incentive value of drugs of abuse. One caveat to conditioned reward studies is the use of a fixed daily dose of the addictive drug during training. However, the transition from…

One possible explanation for attenuation of stress-induced reinstatement of Fix-C CPP is that pre-treatment with MK-801, 7-NI or antalarmin may have suppressed HPA activity and thereby prevented activation of the stress response. This explanation is unlikely since we found that none of the abovementioned pharmacological modulators…