Dissertation
Inhibiting cocaine seeking: infralimbic cortical activity during extinction learning and reinstatement
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2020
DOI: 10.17077/etd.005390
Abstract
Previous work indicates that the infralimbic cortex (IL) mediates extinction learning and actively suppresses cocaine-seeking during reinstatement, following cocaine self-administration. Despite extensive work supporting this role for IL activity, how and under exactly which conditions the IL negatively modulates cocaine-seeking behavior remains unclear. The present experiments utilized optogenetics and in vivo electrophysiology to probe the role of the IL in modulating cocaine seeking following cocaine self-administration. Rats underwent 6 h-access cocaine self-administration followed by home-cage withdrawal or extinction training. Optogenetic manipulations were employed during cocaine seeking sessions and reinstatement. In vivo electrophysiological recordings were conducted during self-administration, extinction and reinstatement.
Results indicated that optogenetic potentiation of IL activity did not alter cocaine seeking following home-cage withdrawal. However, following extinction training, the same manipulation attenuated cocaine seeking. These results suggested that the ability of the IL to attenuate cocaine seeking depends, at least in part, on rats previously having undergone extinction training. Electrophysiological recordings revealed that theta rhythms dominated IL local field potential activity during all experimental stages. During extinction, theta power was lower in trials when cocaine-seeking behaviors were expressed, compared to trials when cocaine seeking was suppressed. These data are consistent with the possibility that IL theta power reflects cognitive control processes, and that lever pressing during extinction is related to diminished cognitive control. Results further indicated heterogeneity in IL single unit activity, including IL pre-motor units the activity of which is predictive of lever pressing or the inhibition thereof. In the context of the existing literature, the present results indicate that inhibiting cocaine seeking is indeed one of the functions of the IL, however this capacity depends on the animal’s learning history and task demands. Furthermore, electrophysiological results suggest modularity in IL activity, which may help explain the inconsistencies observed regarding IL function in relation to different tasks demands.
Details
- Title: Subtitle
- Inhibiting cocaine seeking: infralimbic cortical activity during extinction learning and reinstatement
- Creators
- Victoria Augusta Muller Ewald
- Contributors
- Ryan T LaLumiere (Advisor)Mark Blumberg (Committee Member)John Freeman (Committee Member)Krystal Parker (Committee Member)Jason Radley (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Neuroscience
- Date degree season
- Spring 2020
- Publisher
- University of Iowa
- DOI
- 10.17077/etd.005390
- Number of pages
- xiii, 161 pages
- Copyright
- Copyright 2020 Victoria Augusta Muller Ewald
- Language
- English
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (pages 153-161).
- Public Abstract (ETD)
Cocaine addiction is an exclusively human disorder, despite this, there is value in utilizing rodent models to study the effects of chronic drug use on brain and behavior. In self-administration paradigms, rats learn to press a lever in an operant chamber for a cocaine reward. Following this, rats undergo extinction training where the lever no longer produces a reward, leading to the inhibition of cocaine-seeking behaviors (i.e. lever presses). Over a decade ago, researchers suggested that the infralimbic cortex (IL) decreases cocaine seeking following extinction training. Despite extensive work supporting this role for IL activity, how and under exactly which conditions the IL negatively modulates cocaine-seeking behavior remain unclear.
The present work addressed this lacuna in the literature by potentiating and recording IL activity during cocaine seeking. When IL activity was potentiated, it decreased cocaine seeking only following extinction training, suggesting that the role of the IL in modulating cocaine seeking is task dependent. The present work also recorded IL activity, demonstrating that a pattern of brain activity related to cognitive control was detected in the IL. Results further suggested that during extinction training, the detection of cognitive control activity was closely related to the inhibition of cocaine seeking, suggesting a possible mechanism by which IL activity might inhibit cocaine seeking. Furthermore, electrophysiological results suggested heterogeneity in IL neuronal activity, which may help explain the inconsistencies observed in IL function in relation to different tasks.
- Academic Unit
- Interdisciplinary Graduate Program in Neuroscience
- Record Identifier
- 9983956196002771
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