2010 — 2017 |
Aragona, Brandon Becker, Jill [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Career: Opioid-Dopamine Interactions and Pair Bonding @ University of Michigan Ann Arbor
For many species, including our own, social bonding is essential for numerous aspects of biological and psychological function. Therefore, it is critical to understand the neuroscience underlying social bonding. This project will examine the neurobiology of social bonding by utilizing behavioral, neuroanatomical, and neurochemical assessments of pair bonding in the socially monogamous prairie vole. The experiments will determine how the endogenous opioid systems interact with dopamine signaling in brain circuitry important for reward and motivation underlying pair bond formation and maintenance. Additionally, the project will capitalize on state-of-the-art neurochemical measurement technology (fast-scan cyclic voltammetry) in the prairie vole model to further assess the role of opioid-dopamine interactions in pair bonding. On both intellectual and technical levels, results from these studies are expected to have a tremendous impact on several biological fields. This work focuses on the neuroscience of social bonding, is poised to enhance our understanding of reproduction, ethologically relevant learning and memory, as well as the evolutionary origins of neural mechanisms that mediate social bonding. Importantly, the robust teaching plans will translate into the classroom (at both the graduate and undergraduate levels) and impact how this information will subsequently reach the public domain. Finally, this project provides outstanding training opportunities for both graduate and undergraduate students, revealing details on how students will be trained in the laboratory and placing an emphasis on promoting diversity in neuroscience by the recruitment and training of women and underrepresented minorities into this laboratory.
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0.915 |
2012 — 2016 |
Aragona, Brandon |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Project 2: Individual Variation in Dopamine Transmission and Attribution of Incen
PROJECT SUMMARY (See instructions): One of the primary challenges with the treatment of dmg addiction is that most drug addicts are not able to refrain from taking drugs even though they desperately wish to quit, frequently relapsing even after long periods of abstinence. One powerful trigger for relapse is the presentation of environmental stimuli that were previously associated with drug taking (i.e., a drug-associated cues). Most importantly for this proposal, there is significant individual variation in the degree to which presentation of a drug-associated cue increases the incentive motivation to take drugs. Moreover, the degree that such cues increase the desire to take drug is correlated with how much the cue increases dopamine (DA) transmission, both in PET studies in humans and in preclinical studies in rats. Therefore, rodent studies can be used to study the relationship between the incentive value of drug-cues and DA signaling. In the current application, we propose to measure subsecond changes in DA concentration in freely moving rats and examine the relationship between phasic DA transmission and individual variation in the propensity to attribute incentive value to reward-predictive cues, especially drug-cues. This technology, fast-scan cyclic voltammetry (FSCV), can distinguish between specific aspects of DA transmission (such as release and uptake) and has been used to reveal novel neural consequences of cocaine intake and regional specificity associated with cue-cocaine conditioning. Here, we will use FSCV to determine if there are inherent differences in DA signaling pathways that predict individual variation in the propensity to attribute incentive value to reward-cues. We will then determine how incentive motivation impacts increased DA transmission by reward-predictive cues (including drug-associated cues) and how this is related to individual differences in drug-seeking and relapse. Given the enormous variation in the susceptibility to develop addiction, understanding the neurobiological basis of this susceptibility is critical for treatment of the disease.
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0.915 |
2012 — 2013 |
Aragona, Brandon |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Real-Time Dopamine Transmission During Prairie Vole Social Behavior
DESCRIPTION (provided by applicant): Studies of pair bonding behavior in the monogamous prairie vole have allowed for excellent advances in our understanding of the neurobiology of social attachment. My previous research has used behavioral pharmacology to demonstrate that dopamine (DA) transmission within the nucleus accumbens (NAc) shell is critical for pair bonding. Specifically, my work suggests that during pair bond formation, DA concentration is increased in a manner sufficient to activate high affinity D2-like receptors but not low affinity D-like receptors. Conversely, my previous behavioral pharmacology data also suggest that pair bond maintenance must be associated with high concentration phasic DA release events capable of activating D1-like receptors. Thus, pharmacological studies suggest that specific DA transmission dynamics during social behavior may regulate pair bonding behavior. However, because no prairie lab has ever had the capability to measure real-time DA transmission dynamics, our understanding of in vivo DA transmission during social bonding are quite limited. Here, we will employ fast-scan cyclic voltammetry (FSCV) to provide the first ever sub-second measurements of fluctuations in DA concentration within the NAc shell (and core) of prairie voles during social interactions with known regulation by specific DA receptor subtypes. These studies will test the hypothesis that DA regulation of pair bonding behavior is mediated by presynaptic or postsynaptic mechanisms. Findings from the proposed studies promise to represent significant advances specifically for understanding the neurobiology of social attachment. Additionally, since prairie vole pair bonding represents an ethologically sound form of motivated behavior and motivational learning, these studies will also be of significant importance to our general understanding of the neuroscience of incentive motivation, reward learning, and therefore psychological disorders associated with impairments in social/motivational behaviors regulated by mesolimbic DA transmission. PUBLIC HEALTH RELEVANCE: Mental health problems are often related to impaired social behavior. Here, we will provide the first pre-clinical evidence detailing real-time dopamine transmission during the formation and maintenance of a social attachment. This may prove invaluable for the treatment of mental disorders that are associated with impaired sociality and impaired dopamine function, including social anxiety and depression.
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0.915 |