Search

Your search keyword '"Cippitelli, Andrea"' showing total 214 results
Start Over Author "Cippitelli, Andrea" Language english
214 results on '"Cippitelli, Andrea"'

5. Rare GPR37L1 Variants Reveal Potential Association between GPR37L1 and Disorders of Anxiety and Migraine.

Author

Breitwieser, Gerda E., Cippitelli, Andrea, Yingcai Wang, Pelletier, Oliver, Dershem, Ridge, Jianning Wei, Toll, Lawrence, Fakhoury, Bianca, Brunori, Gloria, Metpally, Raghu, Carey, David J., and Robishaw, Janet

Subjects
*SUMATRIPTAN, *ANXIETY disorders, *MIGRAINE, *MITOGEN-activated protein kinases, *GENETIC variation, *PATHOLOGICAL physiology
Abstract

GPR37L1 is an orphan receptor that couples through heterotrimeric G-proteins to regulate physiological functions. Since its role in humans is not fully defined, we used an unbiased computational approach to assess the clinical significance of rare G-protein-coupled receptor 37-like 1 (GPR37L1) genetic variants found among 51,289 whole-exome sequences from the DiscovEHR cohort. Rare GPR37L1 coding variants were binned according to predicted pathogenicity and analyzed by sequence kernel association testing to reveal significant associations with disease diagnostic codes for epilepsy and migraine, among others. Since associations do not prove causality, rare GPR37L1 variants were functionally analyzed in SK-N-MC cells to evaluate potential signaling differences and pathogenicity. Notably, receptor variants exhibited varying abilities to reduce cAMP levels, activate mitogen-activated protein kinase (MAPK) signaling, and/or upregulate receptor expression in response to the agonist prosaptide (TX14(A)), as compared with the wild-type receptor. In addition to signaling changes, knock-out (KO) of GPR37L1 or expression of certain rare variants altered cellular cholesterol levels, which were also acutely regulated by administration of the agonist TX14(A) via activation of the MAPK pathway. Finally, to simulate the impact of rare nonsense variants found in the large patient cohort, a KO mouse line lacking Gpr37l1 was generated. Although KO animals did not recapitulate an acute migraine phenotype, the loss of this receptor produced sex-specific changes in anxiety-related disorders often seen in chronic migraineurs. Collectively, these observations define the existence of rare GPR37L1 variants associated with neuropsychiatric conditions in the human population and identify the signaling changes contributing to pathological processes. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

19. Role of the satiety factor oleoylethanolamide in alcoholism

Author

Bilbao, Ainhoa, Serrano, Antonia, Cippitelli, Andrea, Pavón, Francisco J., Giuffrida, Andrea, Suárez, Juan, García-Marchena, Nuria, Baixeras, Elena, de Heras, Raquel Gómez, Orio, Laura, Alén, Francisco, Ciccocioppo, Roberto, Cravatt, Benjamin F., Parsons, Loren H., Piomelli, Daniele, and de Fonseca, Fernando Rodríguez

Published
2016
Full Text
View/download PDF

33. Antiobesity effects of the novel in vivo neutral cannabinoid receptor antagonist 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-hexyl-1 H-1,2,4-triazole – LH 21

Author

Pavon, Francisco Javier, Bilbao, Ainhoa, Hernández-Folgado, Laura, Cippitelli, Andrea, Jagerovic, Nadine, Abellán, Gumersindo, Rodríguez-Franco, M <ce:sup loc='post">a</ce:sup> Isabel, Serrano, Antonia, Macias, Manuel, Gómez, Raquel, Navarro, Miguel, Goya, Pilar, and Rodríguez de Fonseca, Fernando

Published
2006
Full Text
View/download PDF

45. Analysis of the distribution of spinal NOP receptors in a chronic pain model using NOP‐eGFP knock‐in mice

Author

Ozawa, Akihiko, Brunori, Gloria, Cippitelli, Andrea, Toll, Nicholas, Schoch, Jennifer, Kieffer, Brigitte L, and Toll, Lawrence

Subjects
Male, Green Fluorescent Proteins, Research Papers, Nociceptin Receptor, Analgesics, Opioid, Mice, Inbred C57BL, Disease Models, Animal, Mice, Opioid Peptides, Spinal Cord, Receptors, Opioid, Animals, Female, Gene Knock-In Techniques, Chronic Pain, Injections, Spinal
Abstract

BACKGROUND AND PURPOSE: The nociceptin/orphanin FQ opioid peptide (NOP) receptor system plays a significant role in the regulation of pain. This system functions differently in the spinal cord and brain. The mechanism by which the NOP receptor agonists regulate pain transmission in these regions is not clearly understood. Here, we investigate the peripheral and spinal NOP receptor distribution and antinociceptive effects of intrathecal nociceptin/orphanin FQ (N/OFQ) in chronic neuropathic pain. EXPERIMENTAL APPROACH: We used immunohistochemistry to determine changes in NOP receptor distribution triggered by spinal nerve ligation (SNL) using NOP‐eGFP knock‐in mice. Antinociceptive effects of intrathecal N/OFQ on SNL‐mediated allodynia and heat/cold hyperalgesia were assessed in wild‐type mice. KEY RESULTS: NOP‐eGFP immunoreactivity was decreased by SNL in the spinal laminae I and II outer, regions that mediate noxious heat stimuli. In contrast, immunoreactivity of NOP‐eGFP was unchanged in the ventral border of lamina II inner, which is an important region for the development of allodynia. NOP‐eGFP expression was also decreased in a large number of primary afferents in the L4 dorsal root ganglion (DRG) of SNL mice. However, SNL mice showed increased sensitivity, compared to sham animals to the effects of i.t administered N/OFQ with respect to mechanical as well as thermal stimuli. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that the spinal NOP receptor system attenuates injury‐induced hyperalgesia by direct inhibition of the projection neurons in the spinal cord that send nociceptive signals to the brain and not by inhibiting presynaptic terminals of DRG neurons in the superficial lamina.

Published
2018

46. Potent and selective NOP receptor activation reduces cocaine self-administration in rats by lowering hedonic set point.

Author

Cippitelli, Andrea, Barnes, Megan, Zaveri, Nurulain T., and Toll, Lawrence

Subjects
*COCAINE, *COCAINE abuse, *NOCICEPTIN, *POINT set theory, *OPIOID receptors, *DRUG utilization
Abstract

Developing new medications for the treatment of cocaine dependence continues to be a research priority. Compelling evidence indicates that mixed opioid receptor agonists, particularly bifunctional compounds that target nociceptin/orphanin FQ peptide (NOP) and mu opioid receptors, may be useful for the treatment of cocaine addiction. Here, we verify that potent and selective pharmacological activation of NOP receptors is sufficient to reduce relevant facets of cocaine addiction in animal models. Accordingly, we determined whether systemic injections of the small molecule AT-312 (0, 1, 3 mg/kg) could reduce operant cocaine self-administration, motivation for cocaine, and vulnerability to cocaine relapse in rats. Results indicate that a potent and selective NOP receptor agonist was equally efficacious in reducing the number of cocaine infusions in short (1-hour), as well as long (6-hour) access sessions. When tested on an economic-demand reinforcement schedule, AT-312 reduced Q0 , the parameter that describes the amount of drug consumed at zero price, while leaving the parameter α, a measure of motivation for drug consumption, unaltered. Furthermore, AT-312 successfully reduced conditioned reinstatement of cocaine seeking. In contrast, the NOP receptor agonist did not modify food self-administration. Blockade of the NOP receptor with the antagonist SB-612111 prevented the effect of AT-312 in decreasing cocaine-reinforced responding under a 2-hour fixed ratio 1 schedule, suggesting a NOP receptor-mediated mechanism. This work demonstrates that potent and selective activation of NOP receptors is sufficient to decrease cocaine taking and seeking behaviors in rats. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

49. Role for the satiety factor Oleoylethanolamide in alcoholism

Author

Bilbao, Ainhoa, Serrano, Antonia, Cippitelli, Andrea, Pavón, Francisco J., Giuffrida, Andrea, Suárez, Juan, García-Marchena, Nuria, Baixeras, Elena, de Heras, Raquel Gomez, Ciccocioppo, Roberto, Cravatt, Benjamin F., Parsons, Loren H., Piomelli, Daniele, and de Fonseca, Fernando Rodríguez

Subjects
Male, Alcoholism, Disease Models, Animal, Mice, Alcohol Drinking, Animals, Oleic Acids, PPAR alpha, Rats, Wistar, Satiety Response, Article, Endocannabinoids, Signal Transduction
Abstract

Oleoylethanolamide (OEA) is a satiety factor released by the gut that controls motivational responses for caloric foods. Here, using both, rat and mice models, we determined that the administration of alcohol releases OEA that, by engaging peroxisome proliferator-activated receptor alpha (PPARα), reduces alcohol consumption. Animals lacking FAAH, the enzyme that degrades OEA, accumulates this lipid in response to ethanol and displayed reduced alcohol preference. Pharmacological administration of OEA reduced operant alcohol self-administration via a peripheral mechanism, since this effect was abrogated by chemical deafferentation with capsaicin. Intracerebral injection of PPARα agonists did not affect alcohol self-administration. OEA also abolished both, cue-induced reinstatement of alcohol self-administration and the enhancement of alcohol consumption induced by a period of alcohol deprivation, suggesting a role for OEA on alcohol relapse. In addition, animals fed with a liquid diet containing 10% alcohol displayed elevated plasma levels of OEA that decreases upon removal of alcohol in the diet. This decrease paralleled the onset of alcohol withdrawal (AWD) symptoms and the administration of OEA reduced the severity of AWD. Finally, OEA, by inhibiting the expression of lipogenic enzymes, reduces chronic alcohol-induced liver steatosis, an effect not observed in PPARα-deficient mice. These results link OEA to the homeostatic adaption to alcohol and opens new opportunities for the treatment of alcoholism.

Published
2015

50. NOP Receptor Antagonists Decrease Alcohol Drinking in the Dark in C57BL/6J Mice.

Author

Brunori, Gloria, Weger, Michelle, Schoch, Jennifer, Targowska‐Duda, Katarzyna, Barnes, Megan, Borruto, Anna Maria, Rorick‐Kehn, Linda M., Zaveri, Nurulain T., Pintar, John E., Ciccocioppo, Roberto, Toll, Lawrence, and Cippitelli, Andrea

Subjects
ANIMAL experimentation, DIET, DRINKING (Physiology), DRINKING behavior, HUMAN locomotion, MICE, MOTOR ability, NARCOTIC antagonists, BINGE drinking, DIETARY sucrose, PHARMACODYNAMICS
Abstract

Background: The nociceptin/orphanin FQ opioid peptide (NOP) receptor and its endogenous ligand N/OFQ have been implicated in the regulation of drug and alcohol use disorders (AUD). In particular, evidence demonstrated that NOP receptor activation blocks reinforcing and motivating effects of alcohol across a range of behavioral measures, including alcohol intake, conditioned place preference, and vulnerability to relapse. Methods: Here, we show the effects of pharmacological activation and inhibition of NOP receptors on binge‐like alcohol consumption, as measured by the "drinking in the dark" (DID) model in C57BL/6J mice. Results: We found that 2 potent and selective NOP agonists AT‐202 (0, 0.3, 1, 3 mg/kg) and AT‐312 (0, 0.3, 1 mg/kg) did not affect binge alcohol drinking at doses that do not affect locomotor activity. AT‐202 also failed to alter DID behavior when administered to mice previously exposed to chronic alcohol treatment with an alcohol‐containing liquid diet. Conversely, treatment with either the high affinity NOP receptor antagonist SB‐612111 (0, 3, 10, 30 mg/kg) or the selective antagonist LY2817412 (0, 3, 10, 30 mg/kg) decreased binge drinking. SB‐612111 was effective at all doses examined, and LY2817412 was effective at 30 mg/kg. Consistently, NOP receptor knockout mice consumed less alcohol compared to wild type. SB‐612111 reduced DID and increased sucrose consumption at doses that do not appear to affect locomotor activity. However, the high dose of SB‐612111 (30 mg/kg) reduced alcohol intake but failed to inhibit preference in a 2‐bottle choice DID model that can assess moderate alcohol intake. Conclusions: The present results suggest that NOP receptor inhibition rather than activation may represent a valuable approach for treatment of AUD characterized by excessive alcohol consumption such as binge drinking. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results