Investigating the Neural Substrates of Relapse Behavior: the Role of the Hippocampus, Bed Nucleus of the Stria Terminalis, and Nucleus Accumbens in Contextual Fear Conditioning and Reinstatement

Reinstatement occurs when exposure to the unconditioned stimulus alone (i.e., context conditioning), after extinction, causes a recovery of responding to the conditioned stimulus. This model is frequently used as a research model of relapse for the treatment of drug abuse and anxiety disorders. Reinstatement of conditioned fear has been shown to depend on the hippocampal formation. The hippocampal formation has also been implicated in the acquisition and expression of contextual freezing. Two experiments examined the role of the hippocampus and two of its efferent targets, the bed nucleus of the stria terminalis (BST) and nucleus accumbens, in two protocols for creating contextual freezing, and the reinstatement of conditioned fear in rats. The results of these experiments suggest that hippocampal-BST neural circuitry is critically involved in the reinstatement effect and the production of a state that is more like anxiety than fear.