Context and neuroinflammation in the posterior dorsomedial striatum impair different aspects of goal-directed decision-making
- Publication Type:
- Thesis
- Issue Date:
- 2023
Open Access
Copyright Clearance Process
- Recently Added
- In Progress
- Open Access
This item is open access.
Compulsive disorders such as substance use disorder and obsessive compulsive disorder are a pervasive problem characterized by the loss of control over one’s actions, resulting in the persistent performance of repetitive behaviours. Preclinical animal models have afforded many important insights into the behavioural mechanisms of compulsive disorders, but these have been limited in scope. For instance, compulsive disorders are known to be chronically relapsing and both human and animal-based studies have suggested that relapse is particularly common following exposure to certain contexts. However, the vast majority of these data have been derived from situations involving a single (active) lever response, whereas in the real world individuals have an array of choices available that lead to multiple outcomes. Therefore, it was the first aim of the current study to use a preclinical rat model to measure how various contexts might affect the propensity to relapse in a two action, two outcome paradigm for the first time. Preclinical studies have also been limited in scope in investigating the brain mechanisms of compulsive disorders. Although multiple studies have identified the neural circuitry of various types of action control and reward-seeking, they have failed to identify the endogenous mechanisms that drives dysfunction in these circuits. Neuroinflammation is a primary candidate, as it has been identified in the striatum of individuals with compulsive disorders; individuals who also display deficits in action selection. Therefore, it was the second aim of this thesis to determine whether neuroinflammation in the posterior dorsomedial striatum (pDMS) causes alterations in cue-guided and goal-directed action selection. Together, the two aims of this thesis combined to comprise the overall aim of my doctoral thesis, which was to investigate the behavioural and brain mechanisms of compulsive disorders in a more ecologically valid manner than current preclinical studies. The results of the experiments presented in this thesis demonstrate, for the first time, that the reinstatement of responding in multiple action-outcome paradigm is primarily context-independent, and that neuroinflammation in the pDMS does alter action control, specifically through the activation of astrocytes, by facilitating it in an aberrant manner. I argue that this process could contribute to compulsivity by causing an excess reliance on goal-directed processes.
Please use this identifier to cite or link to this item: