70 Disruption of reconsolidation,

through either pharmacological intervention or behavioral manipulations, prevents this stabilization and thus weakens or even erases the underlying memory.56,58,69,71 This is, in theory, a potentially more efficacious way to attenuate the excessive fear memories in PTSD than extinction: whereas extinction learning attempts to overlay a set benign memory on top of the traumatic one, disruption of reconsolidation holds the potential to actually erase the underlying traumatic associations. It remains to be seen whether this will prove to be an efficacious strategy for the treatment of check details trauma-associated disorders; data from animals indicating that older, stronger Inhibitors,research,lifescience,medical memories are less susceptible to labilization during recall72,73 suggest that such an intervention may be useful only as secondary prevention in the

aftermath of a traumatic event, Inhibitors,research,lifescience,medical and not as treatment after PTSD is well established. Imbalance between memory systems The multiple memory systems model, now widely accepted, posits that anatomically distinct mnemonic circuits in the mammalian brain subserve qualitatively different types of learning, specialized Inhibitors,research,lifescience,medical for a different type of environmental contingency or context.74 In a complex environment these systems are engaged in parallel and may interact synergistically or, under some circumstances, compete with one another for the control of the organism’s Inhibitors,research,lifescience,medical behavior.74-76 Two of these systems, the spatial/contextual memory system containing the dorsal hippocampus and the fear learning system centered on the basolateral amygdala, have figured prominently in the preceding discussion. An additional system that has been documented to interact with these two

in a variety of circumstances is the striatal habit system. Inhibitors,research,lifescience,medical In rodents, the dorsolateral striatum is essential for the acquisition and execution of inflexible patterns of behavior that automate routine responses to common circumstances.77,78 In certain contexts, habit-driven stimulus-response behaviors compete with more flexible, goal-directed behaviors. This has been shown, for example, in a water maze navigation task, in which disruption of the hippocampus, which is essential for flexible spatial navigation, actually enhances cue-based habit-like learning, while disruptions Linifanib (ABT-869) of striatal function enhance spatial learning.76 An implication of the multiple interacting memory systems is that clinically significant disruptions in adaptive behavior may derive not only from dysfunction or pathological hyperfunction of one or another memory system, but from an imbalance or disrupted regulation of the balance between systems. Recent data and theoretical advances suggest that this is indeed the case in several neuropsychiatric conditions. We close this review with a discussion of two of these. Addiction is a complex disorder that involves pathological alterations to many parts of the brain.