Appropriate behavioral responses to affective stimuli promote health and reduce the chance of harm. However, we often fail to respond appropriately. Obesity results, in part, from the overconsumption of nutrients where our motivation for pleasurable food overrides our homeostatic signals. Exposure to drugs of abuse leads some individuals to consume non-nutritive substances and ignore homeostatic signals. Both diseases involve individuals seeking reward and ignoring negative, aversive consequences. Affective stimuli gain access to motor circuitry by interfacing at the nucleus accumbens (Mogenson et al. 1980). The nucleus accumbens (NAc) and its afferent and efferent connections are critical for behavior directed at rewards. Primary rewarding stimuli evoke changes in neural activity and dopamine (DA) release in the NAc and changes in neural and neurochemical activity in the nucleus accumbens predict behavior directed at reward consumption. Furthermore, pharmacological manipulations of the NAc alter hedonic responses to rewarding stimuli and promote consumption even in the face of negative homeostatic signals. These findings have led some to suggest that the nucleus accumbens is essential for approach behavior and behavior directed at rewarding stimuli. If this is the case, then the NAc and its associated circuitry should behave very differently in response to negative affective stimuli and aversion. Far less is known about how aversive stimuli are processed by these neural elements. Aversive stimuli do seem to alter activity in these regions but in an entirely different manner than aversive stimuli. Behavior is obviously plastic and reflects changes the hedonic valence of affective stimuli through learning and motivational state. We do not know, though, how nucleus accumbens responses are altered when affective stimuli change sign. That is, stimuli can either be devalued or increase in value depending on learned associations and changes in motivational state. This proposal will determine the mechanisms by which the NAc and DA differentially signal reward and aversion. In addition, the proposal will determine plastic changes in neurophysiological and neurochemical signaling within the NAc when the value of affective stimulus changes. This proposal will utilize real-time recordings of NAc activity made during the delivery of positive and negative affective stimuli. The studies proposed here will give valuable insight into normal neural processes underlying changes in value of a given stimulus and thus, shed light on the aberrant signaling underlying disorders of motivational circuitry such as obesity and drug addiction. Aberrant signaling of the mesolimbic system underlie disorders of motivation such as obesity and drug addiction. The major goal of this project is to determine the mechanisms governing mesolimbic signaling in affect and how that signaling is altered by learning and motivational state changes. These studies have the potential for identifying new targets in the treatment of affective disorders.

Public Health Relevance

Aberrant signaling of the mesolimbic system underlie disorders of motivation such as obesity and drug addiction. The major goal of this project is to determine the mechanisms governing mesolimbic signaling in affect and how that signaling is altered by learning and motivational state changes. These studies have the potential for identifying new targets in the treatment of affective disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA025634-05
Application #
8496739
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Lynch, Minda
Project Start
2009-07-15
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$286,019
Indirect Cost
$101,641
Name
University of Illinois at Chicago
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
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Fortin, Samantha M; Chartoff, Elena H; Roitman, Mitchell F (2016) The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors. Neuropsychopharmacology 41:906-15
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Cone, Jackson J; McCutcheon, James E; Roitman, Mitchell F (2014) Ghrelin acts as an interface between physiological state and phasic dopamine signaling. J Neurosci 34:4905-13
Mietlicki-Baase, Elizabeth G; Ortinski, Pavel I; Reiner, David J et al. (2014) Glucagon-like peptide-1 receptor activation in the nucleus accumbens core suppresses feeding by increasing glutamatergic AMPA/kainate signaling. J Neurosci 34:6985-92
McCutcheon, James E; Cone, Jackson J; Sinon, Christopher G et al. (2014) Optical suppression of drug-evoked phasic dopamine release. Front Neural Circuits 8:114
Covey, Dan P; Roitman, Mitchell F; Garris, Paul A (2014) Illicit dopamine transients: reconciling actions of abused drugs. Trends Neurosci 37:200-10

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