Thesis (Ph. D.)--State University of New York at Binghamton, Department of Psychology, 2006. / Includes bibliographical references.

Understanding the process of associative learning between environmental stimuli and cocaine is essential for the prevention of drug-use relapse and long-term treatment of cocaine dependence. Based on contemporary learning theories, empirical studies using natural rewards have shown that cognitive factors, such as uncertainty and prediction errors, play an important role in the process of reward associative learning. Uncertainty is the lack of an accurate predictor for reward while prediction error is defined as the discrepancy between expected and received reward. In this dissertation, we focused on the role of uncertainty and prediction error in cocaine-associative learning. Olfactory and visual cues during self-administration/conditioning sessions were used to induce cocainereward expectation and uncertainty in operant trained catheterized Sprague Dawley rats. The influence of cue-induced uncertainty and prediction error on nucleus accumbens dopamine (NAcc DA) following self-administration of cocaine and saline in these conditioned animals was then measured using in-vivo microdialysis. Results showed that cocaine-stimulated NAcc DA was enhanced in the presence of cues signaling cocaine reward uncertainty (Uncertainty) as compared to animals expecting to get cocaine (Certainty). Also omission of expected cocaine reward (Prediction Error) resulted in a significant depression of NAcc DA levels below baseline. Recently diazepam (a positive GABAA modulator) has been shown to disrupt cocaine-induced LTP and it has been suggested that this disruption can block the acquisition of drug-associated memories. We therefore hypothesized that diazepam-pretreatment during conditioning sessions would disrupt the learned responses to cocaine and saline in the presence of cue-induced uncertainty and prediction error. Our results show that diazepam pretreatment duringconditioning sessions, blocked the differential cocaine-stimulated NAcc DA response to cue-induced certainty and uncertainty. Moreover, on omission of expected cocaine reward (Prediction Error) there was no significant depression of NAcc DA below baseline. The findings of this dissertation thus highlight the importance of cognitive factors (uncertainty and prediction errors) in the process of cocaine-associative learning. They also provide a platform to further explore the influence of these factors on other neuroadaptations during cocaine-associative learning, which will help us develop effective behavioral and pharmacological therapies to prevent drug-use relapse.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 56-58).

Thesis (Ph. D.)--UCLA, 2008. / Vita. Description based on print version record. Includes bibliographical references (leaves 197-220).

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 120-131). Also available in print.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2004. / Bibliography: leaves 85-110.

Thesis (Ph.D.) - University of St Andrews, February 2010.

The problem of this study was to compare performances of college students given relaxation instructions and those not given those instructions on a paired-associate learning task. The results indicated that relaxation instructions alone produced a decrement in recall. When subjects received relaxation instructions as well as the suggestion that relaxation enhances learning, the decrement did not occur. Thus, situational demand characteristics appeared to be a significant variable in determining what effect relaxation instructions had on recall.

The experiment tested the hypothesis that the acetylcholine (ACh) release in the rat auditory cortex is greater in rats undergoing auditory classical conditioning compared to rats in a truly random control paradigm where no associative learning takes place and that this is mediated by prefrontal afferent projections influencing the nucleus basalis magnocellularis (NBM), which in turn modulates ACh release in neocortex. Rats with bilateral ibotenic acid lesions of medial prefrontal and agranular insular cortices were tested in an auditory classical conditioning task while ACh was collected from the primary auditory cortex. It was hypothesized that lesions of these prefrontal areas would prevent learning-related increases of ACh release in the primary auditory cortex. The hypothesized results were supported. Results from this experiment provide unique evidence that medial prefrontal cortex projections to the NBM are important for mediating cortical ACh release during associative learning.

Reinforcement learning occurs when organisms adapt the propensities of given behaviours on the basis of associations with reward and punishment. Currently, reinforcement learning models have been validated in minimalist environments in which only 1-2 environmental stimuli are present as possible predictors of reward. The exception to this is two studies in which the responses of the dopamine system to configurations of multiple stimuli were investigated, however, in both cases the stimuli were presented simultaneously rather than in a sequence. Therefore, we set out to understand how current models of reinforcement learning would respond under more complex conditions in which sequences of events are predictors of reward. In the two experimental chapters of this thesis, we attempted to understand whether midbrain dopaminergic neurons would respond to occasion setters (Chapter 3), and to the overexpectation effect (Chapter 4). In addition, we ran simulations of the behavioural paradigms using temporal difference models of reinforcement learning (Chapter 2) and compared the predictions of the model with the behavioural and neurophysiological data. In Chapter 3, by performing single-neuron recording from VTA and SNpc dopaminergic cells, we demonstrated that our population of neurons were most responsive to the latest predictor of reward, the conditioned stimulus (CS) and not the earliest, the occasion setter (the OS). This is in stark contrast with the predictions of the model (Chapter 2), where the greatest response is seen at the OS onset. We also showed at a neural level that there was only a weak enhancement of the response to the discriminative stimulus (SD) when this was preceded by the OS. On the other hand, at a behavioural level, bar pressing was greatest when the SD was preceded by the OS, demonstrating that rats could use the information provided by the OS, but that dopamine was not controlling the conditioned response. In Chapter 4, our population of dopaminergic neurons showed that they would preferentially respond to only one of the two conditioned stimuli (CSA, CSB) in the overexpectation paradigm. The predictions of the model (Chapter 2) suggested that when the two stimuli would be presented in compound, there would be an inhibitory response if the reward magnitude was kept constant and an excitatory response if the reward magnitude was doubled. The lack of neural firing to one of the two conditioned stimuli, however, does not make for easy interpretation of the data. Perhaps, one of the conditioned stimuli acted as if it were overshadowing the other, resulting in no response to the second CS. Interestingly, at a behavioural level, we did not see increased licking frequency to the compound stimuli presentation, a result that is somewhat at odds with the previous literature. Overall, the results of our experimental chapters suggest that the role that midbrain dopaminergic neurons play in reinforcement learning is more complex than that envisaged by previous investigations.