SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Ciccocioppo Roberto) "

Sökning: WFRF:(Ciccocioppo Roberto)

  • Resultat 1-10 av 12
  • [1]2Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Domi, E., et al. (författare)
  • Further evidence for the involvement of the PPAR gamma system on alcohol intake and sensitivity in rodents
  • 2020
  • Ingår i: Psychopharmacology. - : SPRINGER. - 0033-3158 .- 1432-2072. ; 237, s. 2983-2992
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale Peroxisome Proliferator Activator receptors (PPARs) are intracellular receptors that function as transcription factors, which regulate specific metabolic and inflammatory processes. PPARs are broadly distributed in the body and are also expressed in the central nervous system, especially in areas involved in addiction-related behavioral responses. Recent studies support a role of PPARs in alcoholism and pioglitazone: a PPAR gamma agonist used for treatment of type 2 diabetes showed efficacy in reducing alcohol drinking, stress-induced relapse, and alcohol withdrawal syndrome in rats. Objectives and Methods In the current work, we tested the pharmacological effects of pioglitazone on binge-like alcohol consumption using an intermittent two-bottle choice paradigm in Wistar rats and on the "drinking in the dark" (DID) model in mice with selective deletion of PPAR gamma in neurons. Results Our data show that repeated administration of pioglitazone (10, 30 mg/kg) reduces high voluntary alcohol consumption in Wistar rats. Pre-treatment with the selective PPAR gamma antagonist GW9662 (5 mg/kg) completely prevented the effect of pioglitazone, demonstrating that its action is specifically mediated by activation of PPAR gamma. In line with this result, repeated administration of pioglitazone (30 mg/kg) attenuated binge alcohol consumption in PPAR gamma((+/+)) mice. Whereas in PPAR gamma((-/-)) mice, which exhibit reduced alcohol consumption, pioglitazone had no effect. Of note, PPAR gamma((-/-)) mice exhibited lower patterns of alcohol drinking without showing difference in sucrose (control) intake. Interestingly, PPAR gamma((-/-)) mice displayed a higher sensitivity to the sedative and ataxic effect of alcohol compared with their wild-type counterpart. Conclusions Collectively, these data suggest that PPAR gamma agonists, and specifically pioglitazone, could be potential therapeutics for the treatment of binge alcohol drinking.
  •  
2.
  •  
3.
  • Ciccocioppo, Roberto, et al. (författare)
  • Stress-related neuropeptides and alcoholism : CRH, NPY, and beyond
  • 2009
  • Ingår i: Alcohol. - : Elsevier. - 0741-8329 .- 1873-6823. ; 43:7, s. 491-498
  • Tidskriftsartikel (refereegranskat)abstract
    • This article summarizes the proceedings of a symposium held at the conference on "Alcoholism and Stress: A Framework for Future Treatment Strategies" in Volterra, Italy, May 6-9, 2008. Chaired by Markus Heilig and Roberto Ciccocioppo, this symposium offered a forum for the presentation of recent data linking neuropetidergic neurotransmission to the regulation of different alcohol-related behaviors in animals and in humans. Dr. Donald Gehlert described the development of a new corticotrophin-releasing factor receptor 1 antagonist and showed its efficacy in reducing alcohol consumption and stress-induced relapse in different animal models of alcohol abuse. Dr. Andrey Ryabinin reviewed recent findings in his laboratory, indicating a role of the urocortin 1 receptor system in the regulation of alcohol intake. Dr. Annika Thorsell showed data supporting the significance of the neuropeptide Y receptor system in the modulation of behaviors associated with a history of ethanol intoxication. Dr. Roberto Ciccocioppo focused his presentation on the nociceptin/orphanin FQ (N/OFQ) receptors as treatment targets for alcoholism. Finally, Dr. Markus Heilig showed recent preclinical and clinical evidence suggesting that neurokinin 1 antagonism may represent a promising new treatment for alcoholism. Collectively, these investigators highlighted the significance of neuropeptidergic neurotransmission in the regulation of neurobiological mechanisms of alcohol addiction. Data also revealed the importance of these systems as treatment targets for the development of new medication for alcoholism.
  •  
4.
  • Cippitelli, Andrea, et al. (författare)
  • Pharmacological blockade of corticotropin-releasing hormone receptor 1 (CRH1R) reduces voluntary consumption of high alcohol concentrations in non-dependent Wistar rats
  • 2012
  • Ingår i: Pharmacology, Biochemistry and Behavior. - : Elsevier. - 0091-3057 .- 1873-5177. ; 100:3, s. 522-529
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A dysregulation of the corticotropin-releasing hormone (CRH) system has been implicated in the development of excessive alcohol consumption and dependence. The aim of the present study was to evaluate whether the CRH system is also recruited when non-dependent Wistar rats escalate to high alcohol intake in the intermittent (alternate days) model of drinking.METHODS: We compared intermittent and continuous access to 20% (v/v) alcohol in a two-bottle free choice drinking paradigm. Following a total of twenty 24-hour exposures for every experimental group, we assessed signs of alcohol withdrawal, including anxiety-like behavior and sensitivity to stress. The selective CRH1 receptor (CRH1R) antagonist antalarmin (0, 10, 20 mg/kg, i.p.) was tested on alcohol consumption.RESULTS: Intermittent access to 20% alcohol led non-selected Wistar rats to escalate their voluntary intake to a high and stable level, whereas continuously exposed animals maintained a lower consumption. These groups did not differ in physical withdrawal signs. In addition, no differences were found when anxiogenic-like behavior was studied, neither under basal conditions or following restraint stress. Nevertheless, sensitivity to the treatment with the CRH1R antalarmin was observed since a reduction of 20% alcohol intake was found in both groups of animals regardless of the regimen of alcohol exposure. In addition, antalarmin was effective when injected to animals exposed to intermittent 10% (v/v) alcohol whereas it failed to suppress 10% continuous alcohol intake.CONCLUSIONS: Pharmacological blockade of CRH1R reduced alcohol drinking when sustained high levels of intake were achieved suggesting that the CRH system plays a key role when high doses of ethanol are consumed by non-dependent subjects. This supports the notion that CRH system not only maintains the dependent state but also engages the transition to dependence.
  •  
5.
  • Domi, Esi, et al. (författare)
  • Activation of PPAR gamma Attenuates the Expression of Physical and Affective Nicotine Withdrawal Symptoms through Mechanisms Involving Amygdala and Hippocampus Neurotransmission
  • 2019
  • Ingår i: Journal of Neuroscience. - : SOC NEUROSCIENCE. - 0270-6474 .- 1529-2401. ; 39:49, s. 9864-9875
  • Tidskriftsartikel (refereegranskat)abstract
    • An isoform of peroxisome proliferator-activated receptors (PPARs), PPAR gamma, is the receptor for the thiazolidinedione class of antidiabetic medications including pioglitazone. Neuroanatomical data indicate PPAR gamma localization in brain areas involved in drug addiction. Preclinical and clinical data have shown that pioglitazone reduces alcohol and opioid self-administration, relapse to drug seeking, and plays a role in emotional responses. Here, we investigated the behavioral effect of PPAR gamma manipulation on nicotine withdrawal in male Wistar rats and in male mice with neuron-specific PPAR gamma deletion (PPAR gamma(()(+/+)())) and their littermate wild-type (PPAR gamma((-/-))) controls. Real-time quantitative RT-PCR and RNAscope in situ hybridization assays were used for assessing the levels of expression and cell-type localization of PPAR gamma function, Memory, Mortality, Older subjects, Structural brain abnormalities during nicotine withdrawal. Brain site-specific microinjections of the PPAR gamma agonist pioglitazone were performed to explore the role of this system on nicotine withdrawal at a neurocircuitry level. Results showed that activation of PPAR gamma by pioglitazone abolished the expression of somatic and affective nicotine withdrawal signs in rats and in (PPAR gamma(()(+/+)())) mice. This effect was blocked by the PPAR gamma antagonist GW9662. During early withdrawal and protracted abstinence, the expression of PPAR gamma increased in GABAergic and glutamatergic cells of the amygdala and hippocampus, respectively. Hippocampal microinjections of pioglitazone reduced the expression of the physical signs of withdrawal, whereas excessive anxiety associated with protracted abstinence was prevented by pioglitazone microinjection into the amygdala. Our results demonstrate the implication of the neuronal PPAR gamma in nicotine withdrawal and indicates that activation of PPAR gamma may offer an interesting strategy for smoking cessation.
  •  
6.
  • Domi, Esi, et al. (författare)
  • Genetic Deletion of Neuronal PPAR gamma Enhances the Emotional Response to Acute Stress and Exacerbates Anxiety: An Effect Reversed by Rescue of Amygdala PPAR gamma Function
  • 2016
  • Ingår i: JOURNAL OF NEUROSCIENCE. - : SOC NEUROSCIENCE. - 0270-6474. ; 36:50, s. 12611-12623
  • Tidskriftsartikel (refereegranskat)abstract
    • PPAR gamma is one of the three isoforms of the Peroxisome Proliferator-Activated Receptors (PPARs). PPAR gamma is activated by thiazolidinediones such as pioglitazone and is targeted to treat insulin resistance. PPAR gamma is densely expressed in brain areas involved in regulation of motivational and emotional processes. Here, we investigated the role of PPAR gamma in the brain and explored its role in anxiety and stress responses in mice. The results show that stimulation of PPAR gamma by pioglitazone did not affect basal anxiety, but fully prevented the anxiogenic effect of acute stress. Using mice with genetic ablation of neuronal PPAR gamma (PPAR gamma(NestinCre)), we demonstrated that a lack of receptors, specifically in neurons, exacerbated basal anxiety and enhanced stress sensitivity. The administration of GW9662, a selective PPAR gamma antagonist, elicited a marked anxiogenic response in PPAR gamma wild-type (WT), but not in PPAR gamma(NestinCre) knock-out (KO) mice. Using c-Fos immunohistochemistry, we observed that acute stress exposure resulted in a different pattern of neuronal activation in the amygdala (AMY) and the hippocampus (HIPP) of PPAR gamma(NestinCre) KO mice compared with WT mice. No differences were found between WT and KO mice in hypothalamic regions responsible for hormonal response to stress or in blood corticosterone levels. Microinjection of pioglitazone into the AMY, but not into the HIPP, abolished the anxiogenic response elicited by acute stress. Results also showed that, in both regions, PPAR gamma colocalizes with GABAergic cells. These findings demonstrate that neuronal PPAR gamma is involved the regulation of the stress response and that the AMY is a key substrate for the anxiolytic effect of PPAR gamma
  •  
7.
  • Gehlert, Donald R., et al. (författare)
  • 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine : a novel brain-penetrant, orally available corticotropin-releasing factor receptor 1 antagonist with efficacy in animal models of alcoholism
  • 2007
  • Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 27:10, s. 2718-2726
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe a novel corticotropin-releasing factor receptor 1 (CRF1) antagonist with advantageous properties for clinical development, and its in vivo activity in preclinical alcoholism models. 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (MTIP) inhibited 125I-sauvagine binding to rat pituitary membranes and cloned human CRF1 with subnanomolar affinities, with no detectable activity at the CRF2 receptor or other common drug targets. After oral administration to rats, MTIP inhibited 125I-sauvagine binding to rat cerebellar membranes ex vivo with an ED50 of approximately 1.3 mg/kg and an oral bioavailability of 91.1%. Compared with R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylamino-pyrazolo[1,5-a]pyrimidine) and CP154526 (N-butyl-N-ethyl-4,9-dimethyl-7-(2,4,6-trimethylphenyl)-3,5,7-triazabicyclo[4.3.0]nona-2,4,8,10-tetraen-2-amine), MTIP had a markedly reduced volume of distribution and clearance. Neither open-field activity nor baseline exploration of an elevated plus-maze was affected by MTIP (1-10 mg/kg). In contrast, MTIP dose-dependently reversed anxiogenic effects of withdrawal from a 3 g/kg alcohol dose. Similarly, MTIP blocked excessive alcohol self-administration in Wistar rats with a history of dependence, and in a genetic model of high alcohol preference, the msP rat, at doses that had no effect in nondependent Wistar rats. Also, MTIP blocked reinstatement of stress-induced alcohol seeking both in postdependent and in genetically selected msP animals, again at doses that were ineffective in nondependent Wistar rats. Based on these findings, MTIP is a promising candidate for treatment of alcohol dependence.
  •  
8.
  • Hansson, Anita C., et al. (författare)
  • Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol-Dependent Rats and Humans
  • 2018
  • Ingår i: Neuropsychopharmacology. - : NATURE PUBLISHING GROUP. - 0893-133X .- 1740-634X. ; 43:6, s. 1235-1246
  • Tidskriftsartikel (refereegranskat)abstract
    • Approved pharmacological treatments for alcohol use disorder are limited in their effectiveness, and new drugs that can easily be translated into the clinic are warranted. One of those candidates is oxytocin because of its interaction with several alcohol-induced effects. Alcoholdependent rats as well as post-mortem brains of human alcoholics and controls were analyzed for the expression of the oxytocin system by qRT-PCR, in situ hybridizaton, receptor autoradiography ([(125)l]OVTA binding), and immunohistochemistry. Alcohol self administration and cue-induced reinstatement behavior was measured after intracerebroventicular injection of 10 nM oxytocin in dependent rats. Here we show a pronounced upregulation of oxytocin receptors in brain tissues of alcohol dependent rats and deceased alcoholics, primarily in frontal and striatal areas. This upregulation stems most likely from reduced oxytocin expression in hypothalamic nuclei. Pharmacological validaton showed that oxytocin reduced cue-induced reinstatement response in dependent rats-an effect that was not observed in nondependent rats. Finally, a clinical pilot study (German clinical trial number DRKS00009253) using functional magnetic resonance imaging in heavy social male drinkers showed that intranasal oxytocin (24 IU) decreased neural cue-reactivity in brain networks similar to those detected in dependent rats and humans with increased oxytocin receptor expression. These studies suggest that oxytocin might be used as an anticraving medication and thus may positvely affect treatment outcomes in alcoholics.
  •  
9.
  • Karlsson, Camilla, et al. (författare)
  • Melanin-concentrating hormone receptor 1 (MCH1-R) antagonism : reduced appetite for calories and suppression of addictive-like behaviors
  • 2012
  • Ingår i: Pharmacology, Biochemistry and Behavior. - : Elsevier. - 0091-3057 .- 1873-5177. ; 102:3, s. 400-406
  • Tidskriftsartikel (refereegranskat)abstract
    • RATIONALE: The hypothalamic neuropeptide melanin-concentrating hormone and its MCH1 receptor have been implicated in regulation of feeding and energy homeostasis, as well as modulation of reward-related behaviors. Here, we examined whether the MCH system plays a role both in caloric and motivational aspects of sugar intake.MATERIALS AND METHODS: The non-peptide MCH1-R antagonist GW803430 (3, 10, 30 mg/kg, i.p.) was first tested on self-administration under a fixed ratio schedule of reinforcement of both a caloric (10% w/v sucrose) and a non-caloric (0.06% w/v saccharin) sweet solution. GW803430 was then tested for its ability to alter motivational properties and seeking of sucrose. Lastly, the drug was tested to concurrently examine its effects on the escalated consumption of both sugar and food in animals following intermittent sugar access.RESULTS: The MCH1-R antagonist reduced sucrose- but not saccharin-reinforced lever pressing, likely reflecting a decreased appetite for calories in GW803430-treated rats. GW803430 reduced sucrose self-administration under a progressive ratio schedule, and suppressed cue-induced reinstatement of sucrose seeking, suggesting effects on rewarding properties of sucrose. GW803430 attenuated food intake in rats on intermittent access to sucrose at all doses examined (3, 10, 30 mg/kg), while reduction of sugar intake was weaker in magnitude.CONCLUSION: Together, these observations support an involvement of the MCH system in regulation of energy balance as well as mediation of sucrose reward. MCH may be an important regulator of sugar intake by acting on both caloric and rewarding components.
  •  
10.
  • Ruggeri, Barbara, et al. (författare)
  • Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents
  • 2018
  • Ingår i: Journal of Child Psychology and Psychiatry and Allied Disciplines. - 0021-9630 .- 1469-7610. ; 9:6, s. 50-658
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Nociceptin is a key regulator linking environmental stress and alcohol drinking. In a genome-wide methylation analysis, we recently identified an association of a methylated region in the OPRL1 gene with alcohol-use disorders.METHODS: Here, we investigate the biological basis of this observation by analysing psychosocial stressors, methylation of the OPRL1 gene, brain response during reward anticipation and alcohol drinking in 660 fourteen-year-old adolescents of the IMAGEN study. We validate our findings in marchigian sardinian (msP) alcohol-preferring rats that are genetically selected for increased alcohol drinking and stress sensitivity.RESULTS: We found that low methylation levels in intron 1 of OPRL1 are associated with higher psychosocial stress and higher frequency of binge drinking, an effect mediated by OPRL1 methylation. In individuals with low methylation of OPRL1, frequency of binge drinking is associated with stronger BOLD response in the ventral striatum during reward anticipation. In msP rats, we found that stress results in increased alcohol intake and decreased methylation of OPRL1 in the nucleus accumbens.CONCLUSIONS: Our findings describe an epigenetic mechanism that helps to explain how psychosocial stress influences risky alcohol consumption and reward processing, thus contributing to the elucidation of biological mechanisms underlying risk for substance abuse.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 12
  • [1]2Nästa
 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy