The role of NMDA receptors in the ventral tegmental area in the acquisition of reward -related learning.
Item
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Title
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The role of NMDA receptors in the ventral tegmental area in the acquisition of reward -related learning.
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Identifier
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AAI3325453
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identifier
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3325453
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Creator
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Zellner, Margaret R.
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Contributor
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Adviser: Robert Ranaldi
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Date
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2008
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Language
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English
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Publisher
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City University of New York.
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Subject
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Psychology, Psychobiology
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Abstract
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The ability to learn about conditioned stimuli (CS) associated with rewards is a crucial adaptive mechanism. Activity in the mesocorticolimbic dopamine (DA) system, a well-established neural component in reward-related learning and motivational processes, as well as in the ventral tegmental area (VTA), the source of mesocorticolimbic DA, is correlated with responding to and learning about CSs. The mechanism by which VTA neurons become activated by signals associated with environmental stimuli is currently unknown. This dissertation tested a hypothesis arising from a model suggesting that NMDA receptor stimulation in the VTA allows previously weak glutamate signals carrying putative information about environmental stimuli, coincident with strong excitation correlated with receipt of primary rewards, to be strengthened and thereby acquire the ability to activate VTA neurons in themselves, leading to increased approach behavior. Furthermore, once synaptic strengthening has taken place, the model suggests that NMDA receptor stimulation is not necessary for the expression of reward-related learning. In particular we assessed whether intra-VTA application of AP-5, a selective competitive NMDA receptor antagonist, would impair the acquisition of reward-related learning. Intra-VTA injection of AP-5 impaired the acquisition of lever pressing for food, and the acquisition of conditioned approach. In contrast, AP-5 did not impair the expression of instrumental learning once acquired. Control studies demonstrated that the impairment in learning was not due to reduction in basic food motivation or generalized activity, as separate groups of rats treated with AP-5 did not differ in consumption of rat chow or in ambulatory activity, while showing a mild increase in stereotypy. Analysis of response-reward latencies indicated that any stereotypy that might have occurred during instrumental learning did not cause AP-5 treated rats to experience a reduction in reward contingencies. Finally, rats consuming operant chamber pellets under the influence of intra-VTA AP-5 demonstrated that the reward value of pellets was not impaired by treatment, as AP-5 and control rats emitted similar levels of lever presses for a pellet-associated CS in an extinction session. These findings support the hypothesis that NMDA receptor stimulation in the VTA is necessary for the acquisition, but not expression, of reward-related learning.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
