The SEEKING mind: Primal neuro-affective substrates for appetitive incentive states and their pathological dynamics in addictions and depression
Abstract
Appetitive motivation and incentive states are essential functions sustained by a common emotional brain process, the SEEKING disposition, which drives explorative and approach behaviors, sustains goal-directed activity, promotes anticipatory cognitions, and evokes feelings of positive excitement which control reward-learning. All such functions are orchestrated by the same "archetypical" neural processes, activated in ancient subcortical areas and transported to the forebrain by the mesolimbic dopamine (ML-DA) system. In mammals, the neurophysiology of the SEEKING urge is expressed by DA-promoted high-frequency oscillations, in the form of transient and synchronized gamma waves (>30Hz) emerging in limbic forebrain and diffusing throughout basal ganglia-thalamocortical (BG-T-C) circuits. These patterns may be considered basic "SEEKING neurodynamic impulses" which represent the primary-process exploratory disposition getting integrated with information relative to the external and the internal environment. Abnormal manifestation of SEEKING and its neural substrates are evident in clinical depression and addiction. Specifically, depression is characterized by reduced recruitment of SEEKING, while addictions reflect re-organizations of the SEEKING disposition around ultra-specific appetitive memories and compulsive activities.
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Hedonic dysregulation underlies addiction, stress, and chronic pain, as shown by a shift in the relative salience of natural reward to drug reward in people with severe substance use disorders.
“Though valuation processes are fundamental to survival of the human species, hedonic dysregulation is at the root of an array of clinical disorders, including addiction, stress, and chronic pain, as evidenced by the allostatic shift in the relative salience of natural reward to drug reward observed among persons with severe substance use disorders.”
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- Authors
- Alcaro, A., & Panksepp, J.
- Affiliations
- Fondazione Santa Lucia (IT)
- Washington State University (US)
- Corresponding author
- Alcaro, Antonio
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 35
- Issue
- 9
- Pages
- 1805-1820
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W1980505353
- Cited by
- 240
- References
- 295
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 18 · 2023: 11 · 2022: 10 · 2021: 8 · 2020: 21 · 2019: 40 · 2018: 19 · 2017: 16 · 2016: 13 · 2015: 15 · 2014: 20 · 2013: 11 · 2012: 13
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- appetitive motivation, mesolimbic dopamine system, gamma oscillations, basal ganglia-thalamocortical circuit, reward learning, depression, addiction, appetitive memory, compulsive behavior
- MeSH terms
- Affect, Animals, Appetitive Behavior, Mental Disorders, Depressive Disorder, Biological Evolution, Humans, Learning, Motivation, Nervous System, Nervous System Physiological Phenomena, Neurobiology, Substance-Related Disorders, Drug-Seeking Behavior
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