Examining the role of ventral tegmental area - nucleus accumbens circuit in meditating cocaine seeking behaviors after memory devaluation
Cocaine addiction remains one of the leading health concerns in the United States. Unlike other substances, the development of therapeutic targets for disrupting cocaine seeking behaviors has been limited and ineffective. In this series of studies, I first describe the development of a novel approach that can attenuate cocaine seeking behaviors by devaluing the memory of cocaine reward. Subsequently, I provide evidence of the brain circuitry that underlies memory devaluation of cocaine reward. To examine memory devaluation of cocaine reward, rats received the pairing of cocaine infusions and a light/sound cue during the self-administration training. Subsequently, they underwent cocaine-paired cue exposure in a different context, which would retrieve memories of cocaine reward. Immediately after cue exposure, rats received either saline or lithium chloride (LiCl) injection, inducing temporary gastric illness, in the absence of cocaine. We found that the pairing of memory retrieval of cocaine with LiCl was sufficient to attenuate cocaine seeking behaviors in extinction session the following day, compared to saline pairing control group, which suggested that the memory of cocaine was successfully devalued by LiCl in this approach. Implications of these results indicated that memory devaluation approach could be an effective way to study addiction and disrupt drug seeking behaviors. In addition, we investigated the fundamental role of ventral tegmental area (VTA), containing dopaminergic (DA), GABAergic, and glutamatergic neurons, to nucleus accumbens (NAc) circuit in memory devaluation. The circuit was inhibited by employing a bilateral viral construct with retrograde-cre within NAc and inhibitory hM4Di within VTA. The results indicated that selective inhibition of Gi signaling in designer receptors within VTA-NAc neurons prevented memory devaluation and the reduction in cocaine-seeking. This finding demonstrates that intact VTA-NAc circuit is necessary for disrupting drug seeking -dependent manner.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- In Copyright
- Material Type
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Theses
- Authors
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Mo, Bingxin
- Thesis Advisors
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Johnson, Alexander A.
- Committee Members
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Arguello, Amy A.
Mazei-Robison, Michelle M.
- Date Published
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2024
- Subjects
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Psychology
- Program of Study
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Psychology - Master of Arts
- Degree Level
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Masters
- Language
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English
- Pages
- 41 pages
- Permalink
- https://doi.org/doi:10.25335/2t2b-nw39