Neural degeneration following chronic stimulant abuse reveals a weak link in brain, fasciculus retroflexus, implying the loss of forebrain control circuitry
Abstract
There is increasing evidence that the fasciculus retroflexus (FR) represents a 'weak link' following the continuous administration of drugs of abuse. A variety of drugs which predominantly potentiate dopamine, including D-amphetamine, methamphetamine, MDMA, cocaine, and cathinone, all induce degeneration in axons from lateral habenula, through the sheath of FR, to midbrain cells such as SN, VTA, and raphe. For some drugs, such as cocaine, this is virtually the only degeneration induced in brain. Continuous nicotine also selectively induces degeneration in FR, but in the other half of the tract, i.e. in axons from medial habenula through the core of the tract to interpeduncular nucleus. This phylogenetically primitive tract carries much of the negative feedback from forebrain back onto midbrain reward cells, and the finding that these descending control pathways are compromised following simulated drug binges has implications for theories of drug addiction but also psychosis in general.
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Nicotine causes degeneration of neurons in the fasciculus retroflexus connecting the MHb to the IPN.
“In particular, nicotine causes degeneration of neurons in the portion of the fasciculus retroflexus that connects the MHb to the IPN [77, 78].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [78]
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- Authors
- Ellison, G.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Ellison, G
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 12
- Issue
- 4
- Pages
- 287-297
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W2145913348
- Cited by
- 92
- References
- 60
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 7 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 8 · 2013: 6 · 2012: 4
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- fasciculus retroflexus, lateral habenula, medial habenula, interpeduncular nucleus, axonal degeneration, cocaine, amphetamine, MDMA, cathinone, nicotine, substantia nigra, ventral tegmental area, raphe nuclei, drug addiction, psychosis
- MeSH terms
- Amphetamine, Central Nervous System Stimulants, Animals, Haplorhini, Brain, Cocaine, Humans, Medial Forebrain Bundle, Nerve Degeneration, Neuroanatomy, Nicotine, Prosencephalon, Habenula, Perforant Pathway, Rats
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