This project investigates biopsychological mechanisms of how reward cues trigger intense seeking behavior for their reward. For example, drug cues can cause human addicts to relapse into compulsive drug seeking behavior, even after long abstinence from drug use. We call this phenomenon, cue-triggered 'wanting' of reward, due to excessive attribution of incentive salience to the reward conditioned stimulus. We have developed a behavioral model to study the neurobehavioral mechanism of cue-triggered incentive motivation in rats, the pure conditioned incentive paradigm. Using a natural reward, sucrose, allows exposure of incentive salience 'wanting' mechanisms without contamination by drug withdrawal. We demonstrated that microinjection of amphetamine into nucleus accumbens specifically enhanced cue-triggered 'wanting' for sucrose reward by over 400%. Our behavioral model ruled out alternative explanations for mesolimbic mediation of cue effects (conditioned reinforcement, associative habits, etc.). We have also found that sensitization-related changes caused by prior amphetamine administration leads to a persistent increase in cue-triggered 'wanting' for reward as predicted by the incentive-sensitization hypothesis. In the proposed studies, we will investigate the role of specific dopamine receptors in cue-triggered 'wanting' (using microinjection of specific dopamine agonists and antagonists). We will also clarify the neuroanatomical roles of accumbens shell versus core (in a microinjection mapping experiment and using excitotoxic lesions). Importantly, we will assess whether mesolimbic activation that increase cue-triggered 'wanting' for sucrose also increases 'liking' for sucrose (using the taste reactivity measure of sucrose 'liking'). Finally, we will test the duration of the sensitization-related increase in cue-triggered 'wanting' caused by prior cocaine, amphetamine or morphine administration, and will investigate the interaction of sensitization with mesolimbic activation by drug microinjection. These studies will clarify basic mechanisms of natural cue-triggered 'wanting', and will be useful in understanding mechanisms of cue-triggered relapse in human drug addiction.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BBBP-1 (01))
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Volman, Susan
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University of Michigan Ann Arbor
Schools of Arts and Sciences
Ann Arbor
United States
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Berridge, Kent C (2018) Evolving Concepts of Emotion and Motivation. Front Psychol 9:1647
Cole, Shannon L; Robinson, Mike J F; Berridge, Kent C (2018) Optogenetic self-stimulation in the nucleus accumbens: D1 reward versus D2 ambivalence. PLoS One 13:e0207694
Olney, Jeffrey J; Warlow, Shelley M; Naffziger, Erin E et al. (2018) Current perspectives on incentive salience and applications to clinical disorders. Curr Opin Behav Sci 22:59-69
Badiani, Aldo; Berridge, Kent C; Heilig, Markus et al. (2018) Addiction research and theory: a commentary on the Surgeon General's Report on alcohol, drugs, and health. Addict Biol 23:3-5
Mitchell, Marci R; Berridge, Kent C; Mahler, Stephen V (2018) Endocannabinoid-Enhanced ""Liking"" in Nucleus Accumbens Shell Hedonic Hotspot Requires Endogenous Opioid Signals. Cannabis Cannabinoid Res 3:166-170
Castro, Daniel C; Berridge, Kent C (2017) Opioid and orexin hedonic hotspots in rat orbitofrontal cortex and insula. Proc Natl Acad Sci U S A 114:E9125-E9134
Warlow, Shelley M; Robinson, Mike J F; Berridge, Kent C (2017) Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine. J Neurosci 37:8330-8348
Kringelbach, Morten L; Berridge, Kent C (2017) The Affective Core of Emotion: Linking Pleasure, Subjective Well-Being, and Optimal Metastability in the Brain. Emot Rev 9:191-199
Berridge, Kent C (2017) Is Addiction a Brain Disease? Neuroethics 10:29-33
Song, Cai; Berridge, Kent C; Kalueff, Allan V (2016) 'Stressing' rodent self-grooming for neuroscience research. Nat Rev Neurosci 17:591

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