Matching Items (11)

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Suppressive and Enhancing Effects of Nicotine on Food-Seeking Behavior

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The present study examined how systemic low doses of nicotine affect the microstructure of food-reinforced behavior in rats. Rats were given an acute saline or nicotine treatment (0.1-0.6 mg/kg, resting

The present study examined how systemic low doses of nicotine affect the microstructure of food-reinforced behavior in rats. Rats were given an acute saline or nicotine treatment (0.1-0.6 mg/kg, resting at least 48 h between injections), and a chronic saline or nicotine treatment (0.3 mg/kg for 10 consecutive days). Immediately after treatment, rats were required to press a lever to obtain food, whose availability was unpredictable, but programmed at a constant rate (on average every 80 s). Acute nicotine dose-dependently suppressed behavior prior to the delivery of the first reinforcer, but enhanced food-reinforced behavior afterwards. This effect was primarily observed in the time it took rats to initiate food-seeking behavior, and not in the food-seeking behavior itself. A pre-feeding control procedure suggests that these effects cannot be explained only by changes in appetite. Over the course of chronic nicotine exposure, tolerance developed to the suppressive, but not to the enhancing effects of nicotine on food-seeking behavior. These results suggest that ostensive sensitization effects of nicotine on behavior may instead reflect a tolerance for its suppressive effects on behavior.

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  • 2017-05

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Fos Expression in Response to Nicotine and Social Reward in Adolescent Male Rats

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Previous findings from our lab have demonstrated that nicotine and social reward have synergistic effects when experienced together versus when experienced separately. The purpose of this experiment is to understand

Previous findings from our lab have demonstrated that nicotine and social reward have synergistic effects when experienced together versus when experienced separately. The purpose of this experiment is to understand the neural mechanisms underlying this synergistic effect by quantifying Fos protein, a marker for neural activation, in various brain regions. We utilized the conditioning place preference (CPP) model to assess reward. Four groups of adolescent male rats (n=120) were given either nicotine (Nic) (0.1 mg/kg/mL) or saline (Sal) and were placed in the CPP apparatus either with a social partner (Soc) or alone (Iso). Thus, groups were: 1.)Sal+Iso, 2).Sal+Soc, 3).Nic+Iso, 4).Nic+Soc. Brains of some the rats (n=40) were collected for Fos staining 90 minutes after the last conditioning session to obtain Fos data in response to direct exposure to the stimuli. The following regions were analyzed for Fos expression: central amygdala (CeA), medial amygdala (MeA), basolateral amygdala (BLA), nucleus accumbens core (NAcCore), and nucleus accumbens shell (NAcShell). Place preference changes occurred in socially-conditioned groups reflecting social reward and in nicotine-conditioned groups reflecting nicotine reward. As expected, the Sal+Iso control group failed to display a preference change. Fos data revealed a significant increase in Fos expression in the CeA, MeA, NAcCore and NAcShell for socially-conditioned animals and a significant decrease in the NAcCore for nicotine-conditioned groups. Experiencing both social and nicotine rewards together appeared to produce greater activation in the BLA. However, there was an increase in Fos expression in the negative control group relative to Nic+Iso group. The results of CPP suggest that social, nicotine and their combination are rewarding. The combination of the nicotine and social reward could have been more rewarding than social and nicotine separately, but the test was not sensitive to reward magnitude. The increase in Fos expression in the negative control group in the BLA could be due to isolation stress. Overall, these results suggest that these brain regions had greater activation to social reward.

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  • 2013-05

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Nicotinic Enhancement of Incentive Salience

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Incentive salience is a motivational-cognitive process that can transform an otherwise neutral stimulus into something that is wanted. The prolonged use of nicotine appears to enhance incentive salience; it has

Incentive salience is a motivational-cognitive process that can transform an otherwise neutral stimulus into something that is wanted. The prolonged use of nicotine appears to enhance incentive salience; it has been suggested that the nicotinic enhancement of incentive salience contributes to the potential of relapse in individuals with tobacco addiction. In order to determine whether (a) nicotinic enhancement of incentive salience for non-nicotinic stimuli occurs when rats self-administer nicotine and (b) a history of nicotine use facilitates such enhancement, rats were trained in a morning self-administration paradigm (SA), in combination with an afternoon 4-CS Pavlovian conditioned approach task (PCA) for 24 days. SA was followed by extinction and cue reinstatement. Nicotine SA enhanced incentive salience in the PCA. Upon extinction, incentive salience quickly declined to saline levels, indicating that the nicotinic enhancement of incentive salience is transient. Experimenter-administered nicotine enhanced incentive salience similarly regardless of nicotine history, suggesting that a previous history of nicotine use does sensitize the nicotinic enhancement of incentive salience. Taken together, these results suggest that nicotine must be onboard for the expression of nicotinic enhancement of incentive salience. This suggests that the role of incentive salience in the development and relapse of tobacco addiction may need to be revisited.

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  • 2017-05

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Nicotine Self-Administration and the Social Context

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Research suggests that the more positive the first drug experience, the more likely addiction will develop. Since smoking is initiated in a social setting, it is surprising how little is

Research suggests that the more positive the first drug experience, the more likely addiction will develop. Since smoking is initiated in a social setting, it is surprising how little is known about social context effects on acquisition of nicotine self-administration. We investigated this issue in rats during late adolescence using conjoined self-administration chambers that had a removable shared wall. Rats were assigned to training conditions with either a solid black plexiglass or wire mesh partition in place throughout 22 subsequent 2-hour daily training sessions. Initially, 58 day-old (late-adolescent) male and female rats received 2, 30-min habituation sessions/day over 2 consecutive days, with only an inactive lever present. Sessions began with presentation of a retractable lever and thereafter each response on that lever resulted in simultaneous delivery of saline or 1 of 2 doses of nicotine (0.015 or 0.030 mg/kg, IV) and lever retraction for a 20-second time out. The findings indicate that the social context inhibits nicotine self-administration in female rats during the development of addiction, but has little effect on the initial stages of drug acquisition. Furthermore, the data suggest that in male rats the social context enhances responding independent of nicotine, but has few effects on nicotine self-administration during the development of addiction. The findings have important implications for substance use disorders.

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  • 2015-05

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Modeling ADHD: impulsivity, hyperlocomotion, and sensitivity to nicotine in the SHR strain of rat

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ADHD is a childhood neurobehavioral disorder characterized by inordinate levels of hyperactivity, inattention and impulsivity. The inability to withhold a reinforced response, or response inhibition capacity (RIC), is one aspect

ADHD is a childhood neurobehavioral disorder characterized by inordinate levels of hyperactivity, inattention and impulsivity. The inability to withhold a reinforced response, or response inhibition capacity (RIC), is one aspect of impulsivity associated with ADHD. The first goal of this dissertation was to evaluate the fixed minimum interval (FMI) schedule as a method for assessing RIC. Chapter 2 showed that latencies were substantially more sensitive than FMI-derived estimates of RIC to the effects of pre-feeding and changes in rate and magnitude of reinforcement. Chapter 3 examined the ability of the FMI to discriminate between spontaneously hypertensive rats (SHR), an animal model of ADHD, and Wistar Kyoto (WKY) controls. Results from Chapter 3 showed that RIC was not substantially different between SHR and WKY rats. However, latencies were significantly shorter for SHRs than for WKYs suggesting incentive motivation differed between strains. The second goal of this dissertation was to examine the sensitivity of the SHR to nicotine. ADHD is a risk factor for tobacco dependence. The goal of Chapters 4 and 5 was to determine whether the SHR provided a model of ADHD-related tobacco sensitivity. Chapter 4 examined nicotine's locomotor and rewarding effects in adolescent SHRs using the conditioned place preference (CPP) procedure. SHRs developed CPP to the highest nicotine dose tested and were sensitive to nicotine's locomotor-enhancing properties. WKY controls did not develop CPP to any nicotine dose tested and were not sensitive to nicotine's locomotor properties. However, it is likely that nicotine effects were obscured by a pseudo-conditioning to saline in WKYs. Chapter 5 demonstrated that SHRs were more active than WKYs in the open-field but not in the Rotorat apparatus. Results also showed that SHRs and WKYs were both sensitive to nicotine's locomotor sensitizing effects. However, WKYs were more sensitive than SHRs to nicotine's locomotor suppressing effects. Collectively, results from Chapters 4 and 5 show that SHRs are sensitive to the rewarding and locomotor-enhancing properties of nicotine. However, more research is necessary to confirm that SHRs are a suitable model for studying ADHD-related tobacco use.

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  • 2015

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Analysis of small molecule interactions in biological systems: the study of potential treatments for addiction and disease

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The ability to manipulate the interaction between small molecules and biological macromolecules towards the study of disease pathogenesis has become a very important part of research towards treatment options for

The ability to manipulate the interaction between small molecules and biological macromolecules towards the study of disease pathogenesis has become a very important part of research towards treatment options for various diseases. The work described here shows both the use of DNA oligonucleotides as carriers for a nicotine hapten small molecule, and the use of microsomes to study the stability of compounds derived to treat mitochondrial diseases.

Nicotine addiction is a worldwide epidemic because nicotine is one of the most widely used addictive substances. It is linked to early death, typically in the form of heart or lung disease. A new vaccine conjugate against nicotine held within a DNA tetrahedron delivery system has been studied. For this purpose, several strands of DNA, conjugated with a modified dTpT having three or six carbon atom alkynyl linkers, have been synthesized. These strands have later been conjugated to three separate hapten small molecules to analyze which conjugates formed would be optimal for further testing in vivo.

Mitochondrial diseases are hard to treat, given that there are so many different variations to treat. There is no one compound that can treat all mitochondrial and neurodegenerative diseases; however, improvements can be made to compounds currently under study to improve the conditions of those afflicted. A significant issue leading to compounds failing in clinical trials is insufficient metabolic stability. Many compounds have good biological activity, but once introduced to an animal, are not stable enough to have any effect. Here, several synthesized compounds have been evaluated for metabolic stability, and several showed improved stability, while maintaining biological activity.

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Date Created
  • 2016

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Prosocial influences on nicotine reinforcement, reward, and neural signaling in rodent models

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Social influences are important determinants of drug initiation in humans, particularly during adolescence and early adulthood. My dissertation tested three hypotheses: 1) conditioned and unconditioned nicotine and social rewards

Social influences are important determinants of drug initiation in humans, particularly during adolescence and early adulthood. My dissertation tested three hypotheses: 1) conditioned and unconditioned nicotine and social rewards elicit unique patterns of neural signaling in the corticolimbic neurocircuitry when presented in combination versus individually; 2) play behavior is not necessary for expression of social reward; and 3) social context enhances nicotine self-administration. To test the first hypothesis, Fos protein was measured in response to social and nicotine reward stimuli given alone or in combination and in response to environmental cues associated with the rewards in a conditioned place preference (CPP) test. Social-conditioned environmental stimuli attenuated Fos expression in the nucleus accumbens core. A social partner elevated Fos expression in the caudate-putamen, medial and central amygdala, and both nucleus accumbens subregions. Nicotine decreased Fos expression in the cingulate cortex, caudate-putamen, and the nucleus accumbens core. Both stimuli combined elevated Fos expression in the basolateral amygdala and ventral tegmental area, suggesting possible overlap in processing both rewards in these regions. I tested the second hypothesis with an apparatus containing compartments separated by a wire mesh barrier that allowed limited physical contact with a rat or object. While 2 pairings with a partner rat (full physical contact) produced robust CPP, additional pairings were needed for CPP with a partner behind a barrier or physical contact with an object (i.e., tennis ball). The results demonstrate that physical contact with a partner rat is not necessary to establish social-reward CPP. I tested the third hypothesis with duplex operant conditioning chambers separated either by a solid or a wire mesh barrier to allow for social interaction during self-administration sessions. Nicotine (0.015 and 0.03 mg/kg, IV) and saline self-administration were assessed in male and female young-adult rats either in the social context or isolation. Initially, a social context facilitated nicotine intake at the low dose in male rats, but suppressed intake in later sessions more strongly in female rats, suggesting that social factors exert strong sex-dependent influences on self-administration. These novel findings highlight the importance of social influences on several nicotine-related behavioral paradigms and associated neurocircuitry.

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Date Created
  • 2015

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Effects of nicotine on response inhibition and fos activation in spontaneously hypertensive and wistar kyoto Rats

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Smoking remains the leading cause of preventable death in the United States, and early initiation is associated with greater difficulty quitting. Among adolescent smokers, those with attention-deficit hyperactivity disorder

Smoking remains the leading cause of preventable death in the United States, and early initiation is associated with greater difficulty quitting. Among adolescent smokers, those with attention-deficit hyperactivity disorder (ADHD), characterized by difficulties associated with impulsivity, hyperactivity, and inattention, smoke at nearly twice the rate of their peers. Although cigarette smoking is highly addictive, nicotine is a relatively weak primary reinforcer, spurring research on other potential targets that may maintain smoking, including the potential benefits of nicotine on attention, inhibition, and reinforcer efficacy. The present study employs the most prevalent rodent model of ADHD, the spontaneously hypertensive rat (SHR) and its control comparison Wistar Kyoto (WKY) to examine the effects of acute and chronic subcutaneous nicotine injections on performance in three operant response inhibition paradigms. Functional activation in select regions of the prefrontal cortex and striatum was also explored. Acute (0.1, 0.3, 0.6 mg/kg) and chronic (0.3 mg/kg) nicotine increased impulsive responding regardless of strain, dose, or operant schedule. Dose-dependent decreases in latency to initiate the task were also observed. SHR receiving daily nicotine injections showed less activation in the nucleus accumbens shell compared to saline controls. Despite close similarities, one of the three operant tasks did not detect response inhibition deficits in SHR relative to WKY. A closer examination of these tasks may highlight critical components involved in the amelioration of response inhibition deficits.

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Date Created
  • 2014

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The Relationship Between Nicotine Withdrawal Symptoms and Nicotine Habits in Pilots

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Nicotine and tobacco use, whether it be through cigarette smoking or other devices, creates negative health conditions in pilots. The literature that was reviewed pertained to nicotine withdrawal symptoms and

Nicotine and tobacco use, whether it be through cigarette smoking or other devices, creates negative health conditions in pilots. The literature that was reviewed pertained to nicotine withdrawal symptoms and their negative impact on pilot performance. There have been studies conducted in order to explore how these symptoms impact pilot performance using cigarettes as the only nicotine device and does not specify the nicotine levels or the frequency of use. This thesis extends this work to examine the relationship between the nicotine withdrawal symptoms and the nicotine behaviors of pilots. It was hypothesized that the extent of withdrawal symptoms may differ by device and by nicotine levels and frequency of use, with higher levels and more frequent use being associated with more severe withdrawal symptoms. These behaviors included the device they use to take nicotine whether it be cigarettes, vaporizers, e-cigarettes, or smokeless tobacco. The behaviors also included exploration of how nicotine levels relate to withdrawal symptoms whether the nicotine level is as low as 3mg or high as 36mg. The last relationship that was explored was that between the withdrawal symptoms presented in pilots and how often they used nicotine, whether it be often as every day or less frequent as 1-2 times a year. It was found that there is no statistical relationship between nicotine withdrawal symptoms and the nicotine habits such as device used, nicotine level used, and frequency of use.

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Date Created
  • 2019

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The roles of nicotinic acetylcholine receptors in the ventral tegmental area: implications in nicotine and ethanol addiction and drug intervention

Description

Tobacco and alcohol are the most commonly abused drugs worldwide. Many people smoke and drink together, but the mechanisms of this nicotine (NIC) -ethanol (EtOH) dependence are not fully known.

Tobacco and alcohol are the most commonly abused drugs worldwide. Many people smoke and drink together, but the mechanisms of this nicotine (NIC) -ethanol (EtOH) dependence are not fully known. EtOH has been shown to affect some nicotinic acetylcholine receptors (nAChRs), which potentially underlies NIC-EtOH codependence. Ventral Tegmental Area (VTA) dopamine (DA) and γ-aminobutyric acid (GABA) neurons express different nAChR subtypes, whose net activation results in enhancement of DA release in the Prefrontal Cortex (PFC) and Nucleus Accumbens (NAc). Enhancement of DA transmission in this mesocorticolimbic system is thought to lead to rewarding properties of EtOH and NIC, clarification of which is relevant to public health and clinical diseases. The aim of this study was to elucidate pharmacological mechanisms of action employed by both NIC and EtOH through nAChRs in VTA neurons by evaluating behavioral, network, synaptic and receptor functions therein. It was hypothesized that VTA GABA neurons are controlled by α7 nAChRs on presynaptic GLUergic terminals and α6 nAChRs on presynaptic GABAergic terminals. NIC and EtOH, via these nAChRs, modulate VTA GABA neuronal function. This modulation may underlie NIC and EtOH reward and reinforcement, while pharmacological manipulation of these nAChRs may be a therapeutic strategy to treat NIC or EtOH dependence. This data demonstrates that in VTA GABA neurons, α7 nAChRs on GLUergic terminals play a key role in the mediation of local NIC-induced firing increase. α6*-nAChRs on GABA terminals enhances presynaptic GABA release, and leads to greater inhibition to VTA GABA neurons, which results in an increase VTA DA neuron firing via a disinhibition mechanism. Genetic knockout of these nAChRs significantly prevents EtOH-induced animal conditioned place preference (CPP). Furthermore, levo-tetrahydropalmadine (l-THP), a compound purified from natural Chinese herbs, blocks nAChRs, prevents NIC-induced DA neuronal firing, and eliminates NIC CPP, suggesting it as a promising candidate in a new generation of interventions for smoking cessation. Improved understanding of underlying mechanisms and development of new drugs will increase the number of successful quitters each year and dramatically improve the quality of life for millions suffering from addiction, as well as those around them.

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Date Created
  • 2015