2013 — 2014 |
Mendez, Ian Alfredo |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Effect of Cocaine Sensitization On Cue-Evoked Reward Seeking and Dopamine Release @ University of California Los Angeles
DESCRIPTION (provided by applicant): Environmental cues associated with reward can impact actions and decisions that involve responding for rewards. The influence of environmental cues on action selection is particularly relevant to addiction, in which we see a loss of behavioral control, and increases in habitual drug seeking behavior. Presentation of reward associated cues elicits dopamine (DA) release within the nucleus accumbens (NA), an effect that is believed to underlie increases in reward seeking. The incentive sensitization theory of addiction posits that repeated psychostimulant exposure sensitizes this system, allowing stimuli to more easily activate the DA system and enhance motivation. Thus, drug exposure should allow cues paired with reward to exert greater control over behavior, explaining the sensitive nature of cue-induced drug seeking behavior in addicted individuals. The first objective of the proposed experiments will be to determine, in rats, if cocaine sensitization potentiates cue- evoked reward responding and DA release in the NA and will provide me with training in fast-scan cyclic voltammetry and the Pavlovian-to-instrumental paradigm. The association of a cost with a large reward option can decrease its value and shift choice toward a smaller, less costly reward, and addicted individuals have been repeatedly shown to be more likely to discount larger, more costly rewards, than healthy controls. Interestingly, the presence or absence of reward-related cues appears to shift behavior towards different options. However, it is currently not clear how alterations in cue-evoked DA release, following cocaine sensitization, impacts the effects of cue presence or absence on choice preference. The second objective of the proposed experiments will therefore be to determine how cocaine induced sensitization impacts the effects of reward-associated cues on choice preference, in delay and effort discounting task. Fast-scan cyclic voltammetry will again be used to determine associated changes in dopamine levels within the brain, during cue presentation and choice preference. Impairments in cost-benefit decision making may contribute to addiction by driving behavior towards immediate rewards requiring less effort, such as those associated with drug use (euphoria, relief from withdrawal symptoms), over more effortful, but ultimately more beneficial, rewards associated with abstinence (e.g. - better health, employment, family relationships). Understanding the role of cues, as well as the role of dopamine, in responding for rewards, particularly when different reward-cost options are available, is important to our understanding of how drugs of abuse modify behavior and decision making, as well as for the development of treatment strategies.
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2020 — 2021 |
Mendez, Ian Alfredo |
SC2Activity Code Description: Individual investigator-initiated pilot research projects for faculty at MSIs to generate preliminary data for a more ambitious research project. |
Assessing the Effects of Adolescent Nicotine Vapor Exposure On Motivation and Decision For Rewards @ University of Texas El Paso
Project Summary A lack of information, along with targeted advertising, addition of palatable flavors, and misconceptions about their safety has led to a dramatic increase in the use of electronic nicotine delivery systems (e-cigarettes), with sales of e-cigarettes rising from $20 million in 2008 to $1.5 billion in 2014. In adolescents, continuing annual increases in e-cigarette use have been particularly high and e-cigarette use has now surpassed that of traditional cigarettes within this population. The neurobiology of the adolescent brain produces a behavioral phenotype that increases reward-seeking behavior and makes them engage in more impulsive and risky behaviors, including experimental drug use. These findings warrant a critical need for more research on the effects of nicotine vapor exposure on adolescent health, including its effects on the malleable adolescent brain and the behavior that it controls. We posit that adolescent exposure to nicotine vapor results in long-term dramatic changes in reward seeking behaviors. Based on the results of a limited number of studies investigating the effects of nicotine on decision making and cue-induced motivation for rewards, we predicted that repeated exposure to nicotine vapor will cause a significant and persist increases in impulsive choice, decreases in risky choice, and decreases in cue-induced potentiation of reward seeking behavior, in both male and female rats. Additionally, we expect that specific nicotinic receptor subtypes, particularly within the striatum, will predict reward choice and motivation. We will test these predictions using cost-benefit decision making and Pavlovian- to-instrumental transfer tests with food pellets as the reward. The goal of this research is to determine if exposure to nicotine vapor during adolescence causes significant long-term changes in impulsive or risky choice (Aim 1a) or long-term changes in the ability of reward paired cues to invigorate reward seeking behavior (Aim 1b). Additionally, relationships between reward motivation or reward choice and nicotinic ?4?2 receptor levels in the brains of rats, with and without a history or adolescent nicotine vapor exposure, will be determined (Aim 2). This research will provide immediate and much needed information about this rising and potentially devastating addictive trend, commonly observed in adolescents.
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