Neural Plasticity in the Ventral Tegmental Area, Aversive Motivation during Drug Withdrawal and Hallucinogenic Therapy.
Hector Vargas-Perez, Taryn Elizabeth Grieder, Derek van der Kooy
Journal of Psychoactive Drugs 2023 DOI: 10.1080/02791072.2022.2033889 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Addiction Neuroplasticity |
| Keywords | 5-ht2a Bdnf Hallucinogen Vta Glutamate Psychedelic |
| Key findings | Argues that BDNF-dependent glutamatergic plasticity in the VTA mediates aversive motivation and, when dysregulated, contributes to depression and addiction. Proposes that 5-HT2A receptor activation can reverse drug dependence and BDNF-induced plasticity in animals, suggesting 5-HT2A agonists as potential addiction therapeutics and offering a neurobiological explanation for traditional ceremonial use of 5-HT2A-containing organisms. |
Abstract
Aberrant glutamatergic signaling has been closely related to several pathologies of the central nervous system. Glutamatergic activity can induce an increase in neural plasticity mediated by brain-derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA), a nodal point in the mesolimbic dopamine system. Recent studies have related BDNF dependent plasticity in the VTA with the modulation of aversive motivation to deal with noxious environmental stimuli. The disarray of these learning mechanisms would produce an abnormal augmentation in the representation of the emotional information related to aversion, sometimes even in the absence of external environmental trigger, inducing pathologies linked to mood disorders such as depression and drug addiction. Recent studies point out that serotonin (5-hydroxytryptamine, 5-HT) receptors, especially the 2a (5-HT2a) subtype, play an important role in BDNF-related neural plasticity in the VTA. It has been observed that a single administration of a 5HT2a agonist can both revert an animal to a nondependent state from a drug-dependent state (produced by the chronic administration of a substance of abuse). The 5HT2a agonist also reverted the BDNF-induced neural plasticity in the VTA, suggesting that the administration of 5-HT2a agonists could be used as effective therapeutic agents to treat drug addiction. These findings could explain the neurobiological correlate of the therapeutic use of 5HT2a agonists, which can be found in animals, plants and fungi during traditional medicine ceremonies and rituals to treat mood related disorders.
Comparable studies
Other narrative reviews on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists | 2012 | Review | |
| Towards an understanding of psychedelic-induced neuroplasticity. Review of preclinical and clinical studies | 2023 | Review | |
| Buddha's Brain: Neuroplasticity and Meditation [In the Spotlight] | 2008 | Review | |
| Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics | 2021 | Review | |
| Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms | 2020 | Review |
Citations in the library
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- The psychedelic-peptide paradox: a hormetic hypothesis. Comprehensive Psychoneuroendocrinology June 2, 2025
- Rewarding Effects of the Hallucinogen 4-AcO-DMT Administration and Withdrawal in Rats: A Challenge to the Opponent-Process Theory. Neuroscience Letters January 18, 2024
- Hallucinogenic Therapy in Alzheimer's Disease targeting Mitochondria-Associated Membranes. Neuroscience April 6, 2026
- Ethical challenges in the therapeutic application of classical psychedelics for pediatric health conditions: A comprehensive review Brazilian Journal of Science September 29, 2025
and 1 more in the library
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