Dopamine and μ-opioid receptor dysregulation in the brains of binge-eating female rats – possible relevance in the psychopathology and treatment of binge-eating disorder
Abstract
Adult, female rats given irregular, limited access to chocolate develop binge-eating behaviour with normal bodyweight and compulsive/perseverative and impulsive behaviours similar to those in binge-eating disorder. We investigated whether (a) dysregulated central nervous system dopaminergic and opioidergic systems are part of the psychopathology of binge-eating and (b) these neurotransmitter systems may mediate the actions of drugs ameliorating binge-eating disorder psychopathology. Binge-eating produced a 39% reduction of striatal D 1 receptors with 22% and 23% reductions in medial and lateral caudate putamen and a 22% increase of striatal μ-opioid receptors. There was no change in D 1 receptor density in nucleus accumbens, medial prefrontal cortex or dorsolateral frontal cortex, striatal D 2 receptors and dopamine reuptake transporter sites, or μ-opioid receptors in frontal cortex. There were no changes in ligand affinities. The concentrations of monoamines, metabolites and estimates of dopamine (dopamine/dihydroxyphenylacetic acid ratio) and serotonin/5-hydroxyindolacetic acid ratio turnover rates were unchanged in striatum and frontal cortex. However, turnover of dopamine and serotonin in the hypothalamus was increased ~20% and ~15%, respectively. Striatal transmission via D 1 receptors is decreased in binge-eating rats while μ-opioid receptor signalling may be increased. These changes are consistent with the attenuation of binge-eating by lisdexamfetamine, which increases catecholaminergic neurotransmission, and nalmefene, a μ-opioid antagonist.
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LDX induces activation of dopaminergic and adrenergic receptors DRD1, DRD5, DRD2, ADRA2A, ADRA2B and ADRA2C, contributing to neurotransmission signalling.
“First, LDX induces activation of the known dopaminergic and adrenergic receptors DA receptor 1A (DRD1), DA receptor 1B (DRD5), DRD2, ADRA2A, ADRA2B and alpha-2C adrenergic receptor (ADRA2C) [155, 158, 159], contributing to neurotransmission signalling.”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [158]
The modulation of LDX involves dopaminergic and adrenergic neurotransmission, inducing upregulation of ADRA2A, ADRA2B, ADRA2C, DRD1 and DRD5, and immunomodulation by modulating several interleukins, mainly IL-4 and IL-10 that present an anti-inflammatory profile.
“The modulation of LDX involves dopaminergic and adrenergic neurotransmission, inducing upregulation of ADRA2A, ADRA2B, ADRA2C, DRD1 and DRD5 [155, 158, 159], and immunomodulation by modulating several interleukins, mainly IL-4 and IL-10 that present an anti-inflammatory profile [160].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [158]
DRD1, DRD5, ADRA2A, ADRA2B and ADRA2C are activated downstream by LDX.
“The DRD1, DRD5, ADRA2A, ADRA2B and ADRA2C are activated downstream by LDX [155, 158, 159].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [158]
Cites
Kessler, R. C., Berglund, P. A., Chiu, W. T., Deitz, A. C., Hudson, J. I., Shahly, V., Aguilar-Gaxiola, S., Alonso, J., Angermeyer, M. C., Benjet, C., et al. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.11.020 · Cited by 1,338 · see citing works
The Neuropsychopharmacology of Fronto-Executive Function: Monoaminergic Modulation
Robbins, T. W., & Arnsten, A. F. T. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135535 · Cited by 957 · see citing works
Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks
Arnsten, A. F. T. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.01.027 · Cited by 493 · cited 2× · see citing works
“…reward processing (Delgado, 2007; Balleine et al., 2007), the prefrontal cortex, which mediates attention cognitive function and decision-making (Arnsten, 2001, 2011; Robbins and Arnsten, 2009), and is anatomically linked to the striatum via the striato-cortical pathway (Arnsten, 2001), and…”
BackgroundMcElroy, S. L., Hudson, J., Ferreira-Cornwell, M. C., Radewonuk, J., Whitaker, T., & Gasior, M. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.275 · Cited by 254 · cited 1× · see citing works
“Lisdexamfetamine has been shown to be effective in managing BED in clinical trials (Citrome, 2015; McElroy et al., 2015a, 2016) and was approved in the USA for the treatment of moderate to severe BED in adults (FDA News Release, 2015).”
BackgroundLoss of Control Is Central to Psychological Disturbance Associated With Binge Eating Disorder
Colles, S. L., Dixon, J. B., & O'Brien, P. E. (2008) · Obesity · doi:10.1038/oby.2007.99 · Cited by 235 · see citing works
Evidence for defective mesolimbic dopamine exocytosis in obesity‐prone rats
Geiger, B. M., Behr, G. G., Frank, L. E., Caldera-Siu, A. D., Beinfeld, M. C., Kokkotou, E. G., & Pothos, E. N. (2008) · The FASEB Journal · doi:10.1096/fj.08-110759 · Cited by 194 · see citing works
Bello, N. T., Sweigart, K. L., Lakoski, J. M., Norgren, R., & Hajnal, A. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00716.2002 · Cited by 112 · see citing works
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Quintero, J., Gutiérrez-Casares, J. R., & Álamo, C. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00392-2 · Cited by 70 · see citing works
- Authors
- Heal, D. J., Hallam, M., Prow, M., Gosden, J., Cheetham, S., Choi, Y. K., Tarazi, F., & Hutson, P.
- Affiliations
- RenaSci (United Kingdom) (GB)
- Harvard University (US)
- Teva Pharmaceuticals (United States) (US)
- Corresponding author
- Heal, David J
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2017-04-05
- Volume
- 31
- Issue
- 6
- Pages
- 770-783
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2604619977
- Cited by
- 28
- References
- 7
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 6 · 2018: 2 · 2017: 3
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- binge eating disorder, dopamine, dopamine D1 receptor, mu-opioid receptor, striatum, caudate-putamen, lisdexamfetamine, nalmefene, compulsive eating, serotonin turnover, hypothalamus, female rats, opioid antagonists
- MeSH terms
- Animals, Brain, Bulimia, Dopamine, Female, Naltrexone, Narcotic Antagonists, Psychopathology, Rats, Wistar, Receptors, Dopamine D1, Receptors, Dopamine D2, Receptors, Opioid, mu, Dopamine Plasma Membrane Transport Proteins, Rats, Binge-Eating Disorder
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