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Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. Spring 2017 2017 Neurosciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text Sierra Stringfield Creator Neurobiology Curriculum School of Medicine NICOTINE ENHANCEMENT OF CONDITIONED RESPONDING: INVOLVEMENT OF THE ORBITOFRONTAL CORTEX Nicotine abuse is a substantial public health problem, and one cause of the resilience of nicotine addiction is the influence of conditioned cues. Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. Spring 2017 2017 Neurosciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text Sierra Stringfield Creator Neurobiology Curriculum School of Medicine NICOTINE ENHANCEMENT OF CONDITIONED RESPONDING: INVOLVEMENT OF THE ORBITOFRONTAL CORTEX Nicotine abuse is a substantial public health problem, and one cause of the resilience of nicotine addiction is the influence of conditioned cues. Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. Spring 2017 2017 Neurosciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text Sierra Stringfield Creator Neuroscience Curriculum School of Medicine NICOTINE ENHANCEMENT OF CONDITIONED RESPONDING: INVOLVEMENT OF THE ORBITOFRONTAL CORTEX Nicotine abuse is a substantial public health problem, and one cause of the resilience of nicotine addiction is the influence of conditioned cues. Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. Spring 2017 2017 Neurosciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text Sierra Stringfield Creator Neuroscience Curriculum School of Medicine NICOTINE ENHANCEMENT OF CONDITIONED RESPONDING: INVOLVEMENT OF THE ORBITOFRONTAL CORTEX Nicotine abuse is a substantial public health problem, and one cause of the resilience of nicotine addiction is the influence of conditioned cues. Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. 2017-05 2017 Neurosciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text Sierra Stringfield Creator Neuroscience Curriculum School of Medicine NICOTINE ENHANCEMENT OF CONDITIONED RESPONDING: INVOLVEMENT OF THE ORBITOFRONTAL CORTEX Nicotine abuse is a substantial public health problem, and one cause of the resilience of nicotine addiction is the influence of conditioned cues. Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. 2017 Neurosciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text 2017-05 Sierra Stringfield Creator Neuroscience Curriculum School of Medicine NICOTINE ENHANCEMENT OF CONDITIONED RESPONDING: INVOLVEMENT OF THE ORBITOFRONTAL CORTEX Nicotine abuse is a substantial public health problem, and one cause of the resilience of nicotine addiction is the influence of conditioned cues. Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. 2017 Neurosciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text 2017-05 Sierra Stringfield Creator Neuroscience Curriculum School of Medicine NICOTINE ENHANCEMENT OF CONDITIONED RESPONDING: INVOLVEMENT OF THE ORBITOFRONTAL CORTEX Nicotine abuse is a substantial public health problem, and one cause of the resilience of nicotine addiction is the influence of conditioned cues. Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. 2017 Neurosciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text 2017-05 Sierra Stringfield Creator Neuroscience Curriculum School of Medicine NICOTINE ENHANCEMENT OF CONDITIONED RESPONDING: INVOLVEMENT OF THE ORBITOFRONTAL CORTEX Nicotine abuse is a substantial public health problem, and one cause of the resilience of nicotine addiction is the influence of conditioned cues. Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. 2017 Neurosciences eng Doctor of Philosophy Dissertation Neurobiology Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde W. Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text 2017-05 University of North Carolina at Chapel Hill Degree granting institution Sierra Stringfield Creator Neuroscience Curriculum School of Medicine NICOTINE ENHANCEMENT OF CONDITIONED RESPONDING: INVOLVEMENT OF THE ORBITOFRONTAL CORTEX Nicotine abuse is a substantial public health problem, and one cause of the resilience of nicotine addiction is the influence of conditioned cues. Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. 2017 Neurosciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text 2017-05 Sierra Stringfield Creator Neuroscience Curriculum School of Medicine NICOTINE ENHANCEMENT OF CONDITIONED RESPONDING: INVOLVEMENT OF THE ORBITOFRONTAL CORTEX Nicotine abuse is a substantial public health problem, and one cause of the resilience of nicotine addiction is the influence of conditioned cues. Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. 2017 Neurosciences eng Doctor of Philosophy Dissertation Neurobiology Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde W. Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text 2017-05 University of North Carolina at Chapel Hill Degree granting institution Sierra Stringfield Creator Neuroscience Curriculum School of Medicine NICOTINE ENHANCEMENT OF CONDITIONED RESPONDING: INVOLVEMENT OF THE ORBITOFRONTAL CORTEX Nicotine abuse is a substantial public health problem, and one cause of the resilience of nicotine addiction is the influence of conditioned cues. Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. 2017 Neurosciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde W. Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text 2017-05 Sierra Stringfield Creator Neuroscience Curriculum School of Medicine Nicotine abuse is a substantial public health problem, and one cause of the resilience of nicotine addiction is the influence of conditioned cues. Repeated pairings of an environmental stimulus with a reward, such as the effects of a drug, can lead to the formation of an association between the now conditioned stimulus and the expected outcome. These stimuli are capable of acquiring incentive properties, in which they become appetitive and wanted and are able to motivate behavior. In humans, exposure to these stimuli can result in the expression of a conditioned response, such as experiencing the subjective feeling of craving after exposure to drug-associated cues and attentional bias toward those cues. Pavlovian conditioned approach can be used to model these stimulus-outcome associations in animals. Animals will show conditioned approach responses, and drugs such as nicotine can increase the expression of this behavior. This dissertation will investigate the influence of nicotine on Pavlovian conditioned approach and the neuronal circuitry that contributes to the expression of these behaviors. Specifically, we investigated the orbitofrontal cortex, a region of the prefrontal cortex that is responsible for representing stimulus-outcome associations and influencing behavioral flexibility. Pavlovian conditioned approach was assessed in rats under normal conditions and tested in situations that were designed to challenge the function of the orbitofrontal cortex, to measure the flexibility of conditioned approach, and how nicotine reduced this flexibility. We also investigated the contributions of sex differences to the expression of this behavior, and the expression of BDNF protein after nicotine exposure or conditioned approach training. We found that nicotine enhances Pavlovian conditioned approach in both males and females, and the OFC is involved in expression of this behavior. In addition, nicotine reduces the flexibility of conditioned responses after a change in expected outcome, but did not influence BDNF protein expression. These studies as a whole contribute to our understanding of the ability of nicotine to influence the salience of conditioned cues, hopefully advancing treatment options that focus on reducing the motivational hold that conditioned cues have on smokers who are attempting to remain abstinent. 2017 Neurosciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Donita Robinson Thesis advisor Charlotte Boettiger Thesis advisor Clyde W. Hodge Thesis advisor Regina Carelli Thesis advisor Fulton Crews Thesis advisor text 2017-05 Stringfield_unc_0153D_16992.pdf uuid:820f89b6-329c-4241-81b4-7a26d5772a4f 2017-04-23T13:12:10Z 2019-07-06T00:00:00 proquest application/pdf 3561461 yes