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Current neuropharmacology
2025;23 (4): 458-474.

Cafeteria Diet Abstinence Induces Depressive Behavior and Disrupts Endocannabinoid Signaling in Dopaminergic Areas: A Preclinical Study.

Marialuisa de Ceglia, Adele Romano, Maria Vittoria Micioni Di Bonaventura, Ana Gavito, Luca Botticelli, Emanuela Micioni Di Bonaventura, Marzia Friuli, Carlo Cifani, Fernando Rodríguez de Fonseca, Silvana Gaetani
Author Information
  1. Marialuisa de Ceglia: UGC de Salud Mental y Unidad Clínica de Neurología, Grupo de Neuropsicofarmacología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga, 29010 Málaga, Spain.
  2. Adele Romano: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy.
  3. Maria Vittoria Micioni Di Bonaventura: School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
  4. Ana Gavito: UGC de Salud Mental y Unidad Clínica de Neurología, Grupo de Neuropsicofarmacología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga, 29010 Málaga, Spain.
  5. Luca Botticelli: School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
  6. Emanuela Micioni Di Bonaventura: School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
  7. Marzia Friuli: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy.
  8. Carlo Cifani: School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
  9. Fernando Rodríguez de Fonseca: UGC de Salud Mental y Unidad Clínica de Neurología, Grupo de Neuropsicofarmacología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga, 29010 Málaga, Spain.
  10. Silvana Gaetani: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy.
PMID: 39582223 DOI: 10.2174/1570159X23666241107160840

Abstract

BACKGROUND: Alterations of dopamine (DA) transmission in the brain reward system can be associated with an addictive-like state defined as food addiction (FA), common in obese individuals. Subjects affected by FA experience negative feelings when abstinent from their preferred diet and may develop mood disorders, including depression, sustained by alterations in brain DA pathways.
OBJECTIVE: This study aims to investigate the impact of long-term abstinence from a palatable diet on depressive-like behavior in rats, exploring neurochemical alterations in monoamine and endocannabinoid signaling in DA-enriched brain regions, including ventral tegmental area, dorsolateral striatum, substantia nigra and medial prefrontal cortex.
METHODS: Rats underwent exposure and subsequent abstinence from a palatable cafeteria diet. During abstinence, animals were treated with fatty acid amide hydrolase (FAAH) inhibitor PF-3845 (10 mg/kg, intraperitoneal administration every other day). Lastly, animals were subjected to a forced swimming test, and their brains were dissected and processed for high-performance liquid chromatography measurement of monoamines and western blot analyses of markers of the endocannabinoid machinery.
RESULTS: After the withdrawal from the palatable diet, animals showed depressive-like behavior, coupled with significant variations in the concentration of brain monoamines and in the expression of endocannabinoid signalling machinery proteins in cited brain areas. Treatment with PF-3845 exerted an antidepressant- like effect and restored part of the alterations in monoaminergic and endocannabinoid systems.
CONCLUSION: Overall, our results suggest that abstinence from a cafeteria diet provokes emotional disturbances linked to neuroadaptive changes in monoamines and endocannabinoid signalling in brain areas partaking to DA transmission that could partially be restored by the enhancement of endocannabinoid signalling through FAAH inhibition.

Keywords

Food addiction abstinence cafeteria diet depression dopamine. endocannabinoid system fatty acid amide hydrolase

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Grants

  1. 2012JTX3KL/Italian Ministry of University and Research
  2. CUP B83C22002820006, FP7/PNRR
  3. PI22/00427/Ministerio de Ciencia e Innovación and European Regional Development Funds-European Union (ERDF-EU)
  4. RD21/009/0003/RICORS RIAPAD (Red de Investigación en Atención Primaria en Adicciones)
  5. RD16/0017/000/Programa RETICS Red de Trastornos Adictivos
  6. PND 2022I020/Ministerio de Sanidad, Delegación de Gobierno para el Plan Nacional sobre Drogas
  7. NeuroRECA, RIC-0111-2019/Consejería de Salud y Familia, Junta de Andalucía
  8. PRIN2022LHMF43, CUP J53D23012220001, PRIN 2022SZ2FMK, CUP J53D23012440006/Italian Ministry of University and Research (MUR), by the European Union - NextGenerationEU

MeSH Term

Animals
Endocannabinoids
Male
Rats
Depression
Signal Transduction
Dopamine
Brain
Food Addiction
Amidohydrolases
Rats, Wistar

Chemicals

Endocannabinoids
Dopamine
fatty-acid amide hydrolase
Amidohydrolases
Journal Article

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