Activation of nuclear PPARγ receptors by the antidiabetic agent pioglitazone suppresses alcohol drinking and relapse to alcohol seeking.
paper
Cited
Public
Unavailable
- Authors
- Stopponi, Serena; Somaini, Lorenzo; Cippitelli, Andrea; Cannella, Nazzareno; Braconi, Simone; Kallupi, Marsida; Ruggeri, Barbara; Heilig, Markus; Demopulos, Gregory; Gaitanaris, George; Massi, Maurizio; Ciccocioppo, Roberto
- Year
- 2011
- Journal
- Biological psychiatry
- PMID
- 21276964
- DOI
- 10.1016/j.biopsych.2010.12.010
BACKGROUND: Pioglitazone and rosiglitazone belong to the class of thiazolidinediones (TZDs). They were first developed as antioxidants and then approved for the clinical treatment of insulin resistance and Type 2 diabetes. TZDs bind with high affinity and activate peroxisome proliferator-activated receptor-gamma (PPARγ) receptors, which in the brain are expressed both in neurons and in glia. METHODS: We evaluated the effect of PPARγ activation by TZDs on alcohol drinking, relapse-like behavior, and withdrawal in the rat. We also tested the effect of TZDs on alcohol and saccharin self-administration. RESULTS: We showed that activation of PPARγ receptors by pioglitazone (0, 10, and 30 mg/kg) and rosiglitazone (0, 10 and 30 mg/kg) given orally selectively reduced alcohol drinking. The effect was blocked by pretreatment with the selective PPARγ antagonist GW9662 (5 μg/rat) given into the lateral cerebroventricle, suggesting that this TZD's effect is mediated by PPARγ receptors in the central nervous system. Pioglitazone abolished reinstatement of alcohol seeking, a relapse-like behavior, induced by yohimbine, a pharmacologic stressor, but did not affect cue-induced relapse. In the self-administration experiments, pioglitazone reduced lever pressing for alcohol but not for saccharin. Finally, pioglitazone prevented the expression of somatic signs of alcohol withdrawal. CONCLUSIONS: These findings provide new information about the role of brain PPARγ receptors and identify pioglitazone as candidate treatments for alcoholism and possibly other addictions.
No figures extracted from this document.
No chunks — full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
No citations found.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Cannabinoid-based Pharmacology for the Management of Substance Use Disorders. | Luján MÁ et al. | — | 2026 | → |
| Cannabidiol dose dependently reduces alcohol intake in mice via a non-5-HT<sub>1A</sub> receptor mechanism: Exploration of other potential receptor targets. | Badolato CJ et al. | — | 2025 | → |
| Emerging medications and pharmacological treatment approaches for substance use disorders. | Raymond JS et al. | — | 2025 | → |
| Lanifibranor and semaglutide demonstrate multiple metabolic benefits in free-choice diet induced obese hamster models of MASH and MetALD. | Briand F et al. | — | 2025 | → |
| A reverse translational study of PPAR-α agonist efficacy in human and rodent models relevant to alcohol use disorder. | Mason BJ et al. | — | 2024 | → |
| Molecular mechanisms of morphine tolerance and dependence; novel insights and future perspectives. | Badshah I et al. | — | 2024 | → |
| Neuroimmune modulators as novel pharmacotherapies for substance use disorders. | Grodin EN | — | 2024 | → |
| New insights into the involvement of serotonin and BDNF-TrkB signalling in cannabidiol's antidepressant effect. | Guldager MB et al. | — | 2024 | → |
| Nicotinic regulation of microglia: potential contributions to addiction. | Soares AR et al. | — | 2024 | → |
| Novel medications for problematic alcohol use. | Heilig M et al. | — | 2024 | → |
| Promising immunomodulators for management of substance and alcohol use disorders. | Acuña AM et al. | — | 2024 | → |
| Cue-induced reinstatement of seeking behavior in male rats is independent from the rewarding value of the primary reinforcer: Effect of mGluR5 blockade. | Kallupi M et al. | — | 2023 | → |
| Effects of chronic and binge ethanol administration on mouse cerebellar and hippocampal neuroinflammation. | Niedzwiedz-Massey VM et al. | — | 2023 | → |
| Efficacy of 3 months of additional pioglitazone treatment in type 2 diabetes patients with alcoholic fatty liver disease. | Asakawa M et al. | — | 2023 | → |
| PPARα and PPARγ are expressed in midbrain dopamine neurons and modulate dopamine- and cannabinoid-mediated behavior in mice | Xi Z et al. | — | 2023 | — |
| PPARα and PPARγ are expressed in midbrain dopamine neurons and modulate dopamine- and cannabinoid-mediated behavior in mice. | Hempel B et al. | — | 2023 | → |
| Cannabidiol and substance use disorder: Dream or reality. | Karimi-Haghighi S et al. | — | 2022 | → |
| Effects of a Novel Beta Lactam Compound, MC-100093, on the Expression of Glutamate Transporters/Receptors and Ethanol Drinking Behavior of Alcohol-Preferring Rats. | Alhaddad H et al. | — | 2022 | → |
| Functional interactions between cannabinoids, omega-3 fatty acids, and peroxisome proliferator-activated receptors: Implications for mental health pharmacotherapies. | Jung T et al. | — | 2022 | → |
| Neurobiological Bases of Alcohol Consumption After Social Stress. | Miczek KA et al. | — | 2022 | → |
| Rewarding effect of ethanol-induced conditioned place preference in mice: Effect of the monoterpenoid linalool. | Yunusoğlu O | — | 2022 | → |
| Yohimbine as a pharmacological probe for alcohol research: a systematic review of rodent and human studies. | Curley DE et al. | — | 2022 | → |
| Activation of peroxisome proliferator-activated receptor γ reduces alcohol drinking and seeking by modulating multiple mesocorticolimbic regions in rats. | Fotio Y et al. | — | 2021 | → |
| Andrographis paniculata and Its Main Bioactive Ingredient Andrographolide Decrease Alcohol Drinking and Seeking in Rats Through Activation of Nuclear PPARγ Pathway. | Stopponi S et al. | — | 2021 | → |
| Immune treatments for alcohol use disorder: A translational framework. | Meredith LR et al. | — | 2021 | → |
| Nuclear peroxisome proliferator activated receptor-gamma (PPARγ) as a therapeutic target to treat neurodegeneration and dependence elicited by drugs of abuse. | Ciccocioppo R et al. | — | 2021 | → |
| PGC-1α Signaling Increases GABA(A) Receptor Subunit α2 Expression, GABAergic Neurotransmission and Anxiety-Like Behavior in Mice. | Vanaveski T et al. | — | 2021 | → |
| Reduced alcohol use in patients prescribed pioglitazone. | Dieperink E et al. | — | 2021 | → |
| Resveratrol impairs acquisition, reinstatement and precipitates extinction of alcohol-induced place preference in mice. | Yunusoğlu O | — | 2021 | → |
| The (Poly)Pharmacology of Cannabidiol in Neurological and Neuropsychiatric Disorders: Molecular Mechanisms and Targets. | Vitale RM et al. | — | 2021 | → |
| Argan oil supplementation attenuates voluntary ethanol consumption and withdrawal syndrome promoted by adolescent intermittent ethanol in rat. | El Mostafi H et al. | — | 2020 | → |
| Further evidence for the involvement of the PPARγ system on alcohol intake and sensitivity in rodents. | Domi E et al. | — | 2020 | → |
| Improving translation of animal models of addiction and relapse by reverse translation. | Venniro M et al. | — | 2020 | → |
| Potential of Glial Cell Modulators in the Management of Substance Use Disorders. | Jones JD | — | 2020 | → |
| PPARγ activation by pioglitazone does not suppress cravings for alcohol, and is associated with a risk of myopathy in treatment seeking alcohol dependent patients: a randomized controlled proof of principle study. | Schwandt ML et al. | — | 2020 | → |
| Therapeutic Potential of Peroxisome Proliferator-Activated Receptor (PPAR) Agonists in Substance Use Disorders: A Synthesis of Preclinical and Human Evidence. | Matheson J et al. | — | 2020 | → |
| Activation of PPARγ Attenuates the Expression of Physical and Affective Nicotine Withdrawal Symptoms through Mechanisms Involving Amygdala and Hippocampus Neurotransmission. | Domi E et al. | — | 2019 | → |
| Building better strategies to develop new medications in Alcohol Use Disorder: Learning from past success and failure to shape a brighter future. | Cannella N et al. | — | 2019 | → |
| Its complicated: The relationship between alcohol and microglia in the search for novel pharmacotherapeutic targets for alcohol use disorders. | Melbourne JK et al. | — | 2019 | → |
| Neuroimmune signaling in alcohol use disorder. | Erickson EK et al. | — | 2019 | → |
| Neuroinflammation in addiction: A review of neuroimaging studies and potential immunotherapies. | Kohno M et al. | — | 2019 | → |
| Alcohol, adipose tissue and liver disease: mechanistic links and clinical considerations. | Parker R et al. | — | 2018 | → |
| Anti-stress neuropharmacological mechanisms and targets for addiction treatment: A translational framework. | Greenwald MK | — | 2018 | → |
| Assessment of pioglitazone and proinflammatory cytokines during buprenorphine taper in patients with opioid use disorder. | Schroeder JR et al. | — | 2018 | → |
| Ethanol and Cytokines in the Central Nervous System. | Roberto M et al. | — | 2018 | → |
| Inhibition of fatty acid amide hydrolase in the central amygdala alleviates co-morbid expression of innate anxiety and excessive alcohol intake. | Stopponi S et al. | — | 2018 | → |
| Investigational drugs for alcohol use disorders: a review of preclinical data. | Ch'Ng SS et al. | — | 2018 | → |
| Medications for alcohol use disorders: An overview. | Akbar M et al. | — | 2018 | → |
| Microglia and alcohol meet at the crossroads: Microglia as critical modulators of alcohol neurotoxicity. | Henriques JF et al. | — | 2018 | → |
| Peroxisome Proliferator Activated Receptor Agonists Modulate Transposable Element Expression in Brain and Liver. | Ferguson LB et al. | — | 2018 | → |
| PPARγ agonism attenuates cocaine cue reactivity. | Miller WR et al. | — | 2018 | → |
| Role of the innate immune system in the neuropathological consequences induced by adolescent binge drinking. | Pascual M et al. | — | 2018 | → |
| The PPARγ Agonist Pioglitazone Fails to Alter the Abuse Potential of Heroin, But Does Reduce Heroin Craving and Anxiety. | Jones JD et al. | — | 2018 | → |
| Transcriptional Regulators as Targets for Alcohol Pharmacotherapies. | Savarese AM et al. | — | 2018 | → |
| An assessment of the utilization of the preclinical rodent model literature in clinical trials of putative therapeutics for the treatment of alcohol use disorders. | Barajaz AM et al. | — | 2017 | → |
| Genetic studies of alcohol dependence in the context of the addiction cycle. | Reilly MT et al. | — | 2017 | → |
| Medications development for the treatment of alcohol use disorder: insights into the predictive value of animal and human laboratory models. | Yardley MM et al. | — | 2017 | → |
| Pioglitazone, a PPARγ agonist, reduces nicotine craving in humans, with marginal effects on abuse potential. | Jones JD et al. | — | 2017 | → |
| Pioglitazone attenuates the opioid withdrawal and vulnerability to relapse to heroin seeking in rodents. | de Guglielmo G et al. | — | 2017 | → |
| Promising pharmacogenetic targets for treating alcohol use disorder: evidence from preclinical models. | Rinker JA et al. | — | 2017 | → |
| Protection against alcohol-induced neuronal and cognitive damage by the PPARγ receptor agonist pioglitazone. | Cippitelli A et al. | — | 2017 | → |
| Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. | Hallahan B et al. | — | 2016 | → |
| Emerging targets for addiction neuropharmacology: From mechanisms to therapeutics. | Ubaldi M et al. | — | 2016 | → |
| Ethanol-induced changes in poly (ADP ribose) polymerase and neuronal developmental gene expression. | Gavin DP et al. | — | 2016 | → |
| Evaluation of TLR4 Inhibitor, T5342126, in Modulation of Ethanol-Drinking Behavior in Alcohol-Dependent Mice. | Bajo M et al. | — | 2016 | → |
| Genetic Deletion of Neuronal PPARγ Enhances the Emotional Response to Acute Stress and Exacerbates Anxiety: An Effect Reversed by Rescue of Amygdala PPARγ Function. | Domi E et al. | — | 2016 | → |
| Impact of the Innate Immune Response in the Actions of Ethanol on the Central Nervous System. | Montesinos J et al. | — | 2016 | → |
| Inflammatory responses to alcohol in the CNS: nuclear receptors as potential therapeutics for alcohol-induced neuropathologies. | Kane CJ et al. | — | 2016 | → |
| Localization of PPAR isotypes in the adult mouse and human brain. | Warden A et al. | — | 2016 | → |
| Peroxisome proliferator-activated receptor-gamma dependent pathway reduces the phosphorylation of dynamin-related protein 1 and ameliorates hippocampal injury induced by global ischemia in rats. | Chuang YC et al. | — | 2016 | → |
| Peroxisome Proliferator-Activated Receptor-γ Agonists: Potential Therapeutics for Neuropathology Associated with Fetal Alcohol Spectrum Disorders. | Drew PD et al. | — | 2016 | → |
| PPAR Agonists: I. Role of Receptor Subunits in Alcohol Consumption in Male and Female Mice. | Blednov YA et al. | — | 2016 | → |
| Preclinical Medication Development: New Targets and New Drugs. | Kasten CR et al. | — | 2016 | → |
| Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking. | Galesi FL et al. | — | 2016 | → |
| Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress. | Mantsch JR et al. | — | 2016 | → |
| The effects of pioglitazone, a PPARγ receptor agonist, on the abuse liability of oxycodone among nondependent opioid users. | Jones JD et al. | — | 2016 | → |
| Investigational therapies for the pharmacological treatment of alcoholism. | Hillemacher T et al. | — | 2015 | → |
| Peroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans. | Blednov YA et al. | — | 2015 | → |
| Pioglitazone prevents morphine antinociceptive tolerance via ameliorating neuroinflammation in rat cerebral cortex. | Ghavimi H et al. | — | 2015 | → |
| PPARα Agonists Reduce Alcohol Drinking: Do They Act in the Brain or in the Liver? | Karahanian E et al. | — | 2015 | → |
| PPARγ activation attenuates opioid consumption and modulates mesolimbic dopamine transmission. | de Guglielmo G et al. | — | 2015 | → |
| PPARγ ligands and their therapeutic applications: a patent review (2008 - 2014). | Takada I et al. | — | 2015 | → |
| Protective effect of pioglitazone on morphine-induced neuroinflammation in the rat lumbar spinal cord. | Charkhpour M et al. | — | 2015 | → |
| Analgesic tolerance to morphine is regulated by PPARγ. | de Guglielmo G et al. | — | 2014 | → |
| Combined pharmacotherapies for the management of alcoholism: rationale and evidence to date. | Lee MR et al. | — | 2014 | → |
| Ethanol intake and ethanol-conditioned place preference are reduced in mice treated with the bioflavonoid agent naringin. | Bahi A et al. | — | 2014 | → |
| Fetal alcohol spectrum disorders and neuroimmune changes. | Drew PD et al. | — | 2014 | → |
| Molecular basis of alcoholism. | Most D et al. | — | 2014 | → |
| Neuroimmune pathways in alcohol consumption: evidence from behavioral and genetic studies in rodents and humans. | Robinson G et al. | — | 2014 | → |
| Opportunities for the development of neuroimmune therapies in addiction. | Ray LA et al. | — | 2014 | → |
| Pharmacotherapy for alcoholic patients with alcoholic liver disease. | Vuittonet CL et al. | — | 2014 | → |
| Pioglitazone prevents morphine antinociception tolerance and withdrawal symptoms in rats. | Ghavimi H et al. | — | 2014 | → |
| PPAR agonists regulate brain gene expression: relationship to their effects on ethanol consumption. | Ferguson LB et al. | — | 2014 | → |
| Role of cues and contexts on drug-seeking behaviour. | Perry CJ et al. | — | 2014 | → |
| The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice. | Al Mansouri S et al. | — | 2014 | → |
| Activation of PPARγ by pioglitazone potentiates the effects of naltrexone on alcohol drinking and relapse in msP rats. | Stopponi S et al. | — | 2013 | → |
| Dual role of PPAR-γ in induction and expression of behavioral sensitization to cannabinoid receptor agonist WIN55,212-2. | Enayatfard L et al. | — | 2013 | → |
| Gut peptide GLP-1 and its analogue, Exendin-4, decrease alcohol intake and reward. | Shirazi RH et al. | — | 2013 | → |
| Inhibition of FAAH and activation of PPAR: new approaches to the treatment of cognitive dysfunction and drug addiction. | Panlilio LV et al. | — | 2013 | → |
| Modeling relapse in animals. | Martin-Fardon R et al. | — | 2013 | → |
| Neuroimmune signaling: a key component of alcohol abuse. | Mayfield J et al. | — | 2013 | → |
| Peroxisome proliferator-activated receptor (PPAR) agonists as promising new medications for drug addiction: preclinical evidence. | Le Foll B et al. | — | 2013 | → |
| Role of a genetic polymorphism in the corticotropin-releasing factor receptor 1 gene in alcohol drinking and seeking behaviors of marchigian sardinian alcohol-preferring rats. | Ayanwuyi LO et al. | — | 2013 | → |
| Development of novel pharmacotherapeutics for tobacco dependence: progress and future directions. | Harmey D et al. | — | 2012 | → |
| Glial modulators: a novel pharmacological approach to altering the behavioral effects of abused substances. | Cooper ZD et al. | — | 2012 | → |
| Mifepristone in the central nucleus of the amygdala reduces yohimbine stress-induced reinstatement of ethanol-seeking. | Simms JA et al. | — | 2012 | → |
| Neuroimmune mechanisms in fetal alcohol spectrum disorder. | Kane CJ et al. | — | 2012 | → |
| Plasma Endocannabinoid Alterations in Individuals with Substance Use Disorder are Dependent on the "Mirror Effect" of Schizophrenia. | Desfossés J et al. | — | 2012 | → |
| Common cellular and molecular mechanisms in obesity and drug addiction. | Kenny PJ | — | 2011 | → |
| Induction of multiple reinstatements of ethanol- and sucrose-seeking behavior in Long-Evans rats by the α-2 adrenoreceptor antagonist yohimbine. | Simms JA et al. | — | 2011 | → |
| The Endocannabinoid System as Pharmacological Target Derived from Its CNS Role in Energy Homeostasis and Reward. Applications in Eating Disorders and Addiction. | Viveros MP et al. | — | 2011 | → |