Understanding the neural mechanisms underlying the extinction of maladaptive
behaviors has become increasingly relevant. Extinction, or the reduction of a response
due to lack of reinforcement, is believed to be “new learning.” Most extinction paradigms
involve the performance of the previously reinforced response in the absence of
reinforcement in order for extinction to occur. Conversely, latent extinction is a cognitive
form of learning in which the previously rewarded response is not made during extinction
training. However, until now the neurobiological basis of latent extinction has remained
unknown.
This dissertation has three aims to examine the neurobiological basis of latent
extinction. Previous research has shown latent extinction to be impaired following
hippocampal inactivation and the goal of Aim 1 was to examine other neural systems
potentially involved in latent extinction through examination of brain structures such as
the dorsal striatum, medial prefrontal cortex, and basolateral amygdala. Additionally, the
neurochemical basis of latent extinction is unidentified; therefore Aim 2 addressed this
question, specifically investigating the glutamatergic system through both NMDA receptor agonism and antagonism. Finally, understanding latent extinction may be useful
for the extinction of drug addiction. Aim 3 was to examine some clinical implications for
the extinction of drug addiction utilizing latent extinction following maze running for an
oral cocaine reward.
Reversible neural inactivation studies using the sodium channel blocker
bupivacaine demonstrated a selective impairment of response extinction following dorsal
striatum inactivation, but no effect on either latent or response extinction following
medial prefrontal cortex or basolateral amygdala inactivation. These results, coupled with
previous data from our lab demonstrate a double dissociation for extinction behavior.
Further, peripheral NMDA receptor agonism with D-cyloserine enhances latent
extinction and intra-hippocampal NMDA receptor antagonism with AP5 impairs latent
extinction, identifying a role for the glutamatergic system in latent extinction. Finally,
oral cocaine administration during acquisition selectively impairs latent extinction
indicating that drug use affects the relive use of multiple memory systems during
extinction. Overall, the multiple memory systems theory and latent extinction provide a
framework with which to further understand the neural mechanisms of extinction
behavior.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2823 |
| Date | 15 May 2009 |
| Creators | Gabriele, Amanda |
| Contributors | Packard, Mark G. |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | electronic, application/pdf, born digital |
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