The CCKB antagonist CI988 reduces food intake in fasted rats via a dopamine mediated pathway

Frommelt, Lisa; Lembke, Vanessa; Hofmann, Tobias; Goebel-Stengel, Miriam; Mönnikes, Hubert; Wiedenmann, Bertram; Klapp, Burghard F.; Stengel, Andreas; Kobelt, Peter

doi:10.1016/j.peptides.2012.11.012

Cited by 10 publications

(2 citation statements)

References 34 publications

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“…Interestingly, CCK-2R activity may play a role in mediating central dopaminergic system in regulating food intake. Indeed CCK-2R antagonists reduce food intake, indicating that shifts toward CCK-2R activity in OLETF rats may lead to hyperphagia via downstream DA signaling pathways [60].…”

Section: Sucrose Food Intake and Body Weightmentioning

confidence: 99%

Reduced Striatal Dopamine Transporter Availability and Heightened Response to Natural and Pharmacological Stimulation in CCK-1R-Deficient Obese Rats

Hamamah

Hajnal

Covașă

2023

IJMS

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Alterations in dopamine neurotransmission are associated with obesity and food preferences. Otsuka Long-Evans Tokushima Fatty (OLETF) rats that lack functional cholecystokinin receptor type-1 (CCK-1R), due to a natural mutation, exhibit impaired satiation, are hyperphagic, and become obese. In addition, compared to lean control Long-Evans Tokushima (LETO) rats, OLETF rats have pronounced avidity for over-consuming palatable sweet solutions, have greater dopamine release to psychostimulants, reduced dopamine 2 receptor (D2R) binding, and exhibit increased sensitivity to sucrose reward. This supports altered dopamine function in this strain and its general preference for palatable solutions such as sucrose. In this study, we examined the relationship between OLETF’s hyperphagic behavior and striatal dopamine signaling by investigating basal and amphetamine stimulated motor activity in prediabetic OLETF rats before and after access to sucrose solution (0.3 M) compared to non-mutant control LETO rats, as well as availability of dopamine transporter (DAT) using autoradiography. In the sucrose tests, one group of OLETF rats received ad libitum access to sucrose while the other group received an amount of sucrose equal to that consumed by the LETO. OLETFs with ad libitum access consumed significantly more sucrose than LETOs. Sucrose exerted a biphasic effect on basal activity in both strains, i.e., reduced activity for 1 week followed by increased activity in weeks 2 and 3. Basal locomotor activity was reduced (−17%) in OLETFs prior to sucrose, compared to LETOs. Withdrawal of sucrose resulted in increased locomotor activity in both strains. The magnitude of this effect was greater in OLETFs and the activity was increased in restricted compared to ad-libitum-access OLETFs. Sucrose access augmented AMPH-responses in both strains with a greater sensitization to AMPH during week 1, an effect that was a function of the amount of sucrose consumed. One week of sucrose withdrawal sensitized AMPH-induced ambulatory activity in both strains. In OLETF with restricted access to sucrose, withdrawal resulted in no further sensitization to AMPH. DAT availability in the nucleus accumbens shell was significantly reduced in OLETF compared with aged-matched LETO. Together, these findings show that OLETF rats have reduced basal DA transmission and a heightened response to natural and pharmacological stimulation.

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Section: Sucrose Food Intake and Body Weightmentioning

confidence: 99%

Reduced Striatal Dopamine Transporter Availability and Heightened Response to Natural and Pharmacological Stimulation in CCK-1R-Deficient Obese Rats

Hamamah

Hajnal

Covașă

2023

IJMS

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“…CCK2R receptor-deficient mice exhibit significantly increased food intake compared with wildtype mice (Clerc et al, 2007;Miyasaka et al, 2002;Weiland et al, 2004), elevated body weight (Chen et al, 2006), signs of obesity (Weiland et al, 2004) as well as increased plasma levels of insulin and leptin (Cano et al, 2003;Clerc et al, 2007). In contrast to the above-mentioned studies, ICV injection with specific CCK2R antagonists inhibits food intake in rats (Corp et al, 1997;Frommelt et al, 2013). Also, in another genetic investigation, CCK2R-deficient mice exhibited normal eating behavior and body weight gain (Kopin et al, 1999).…”

Section: Discussionmentioning

confidence: 98%

Role of Cholecystokinin in Anorexia Induction Following Oral Exposure to the 8-Ketotrichothecenes Deoxynivalenol, 15-Acetyldeoxynivalenol, 3-Acetyldeoxynivalenol, Fusarenon X, and Nivalenol

Zhou

et al. 2014

Toxicological Sciences

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Cereal grain contamination by trichothecene mycotoxins is known to negatively impact human and animal health with adverse effects on food intake and growth being of particular concern. The head blight fungus Fusarium graminearum elaborates five closely related 8-ketotrichothecene congeners: (1) deoxynivalenol (DON), (2) 3-acetyldeoxynivalenol (3-ADON), (3) 15-acetyldeoxynivalenol (15-ADON), (4) fusarenon X (FX), and (5) nivalenol (NIV). While anorexia induction in mice exposed intraperitoneally to DON has been linked to plasma elevation of the satiety hormones cholecystokinin (CCK) and peptide YY₃₋₃₆ (PYY₃₋₃₆), the effects of oral gavage of DON or of other 8-keotrichothecenes on release of these gut peptides have not been established. The purpose of this study was to (1) compare the anorectic responses to the aforementioned 8-ketotrichothecenes following oral gavage at a common dose (2.5 mg/kg bw) and (2) relate these effects to changes plasma CCK and PYY₃₋₃₆ concentrations. Elevation of plasma CCK markedly corresponded to anorexia induction by DON and all other 8-ketotrichothecenes tested. Furthermore, the CCK1 receptor antagonist SR 27897 and the CCK2 receptor antagonist L-365,260 dose-dependently attenuated both CCK- and DON-induced anorexia, which was consistent with this gut satiety hormone being an important mediator of 8-ketotrichothecene-induced food refusal. In contrast to CCK, PYY₃₋₃₆ was moderately elevated by oral gavage with DON and NIV but not by 3-ADON, 15-ADON, or FX. Taken together, the results suggest that CCK plays a major role in anorexia induction following oral exposure to 8-ketotrichothecenes, whereas PYY₃₋₃₆ might play a lesser, congener-dependent role in this response.

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Neuroendocrine Peptides of the Gut and Their Role in the Regulation of Food Intake

Schalla

Taché

Stengel

2021

Comprehensive Physiology

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The regulation of food intake encompasses complex interplays between the gut and the brain. Among them, the gastrointestinal tract releases different peptides that communicate the metabolic state to specific nuclei in the hindbrain and the hypothalamus. The present overview gives emphasis on seven peptides that are produced by and secreted from specialized enteroendocrine cells along the gastrointestinal tract in relation with the nutritional status. These established modulators of feeding are ghrelin and nesfatin-1 secreted from gastric X/A-like cells, cholecystokinin (CCK) secreted from duodenal I-cells, glucagon-like peptide 1 (GLP-1), oxyntomodulin, and peptide YY (PYY) secreted from intestinal L-cells and uroguanylin (UGN) released from enterochromaffin (EC) cells.

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The CCKB antagonist CI988 reduces food intake in fasted rats via a dopamine mediated pathway

Cited by 10 publications

References 34 publications

Reduced Striatal Dopamine Transporter Availability and Heightened Response to Natural and Pharmacological Stimulation in CCK-1R-Deficient Obese Rats

Reduced Striatal Dopamine Transporter Availability and Heightened Response to Natural and Pharmacological Stimulation in CCK-1R-Deficient Obese Rats

Role of Cholecystokinin in Anorexia Induction Following Oral Exposure to the 8-Ketotrichothecenes Deoxynivalenol, 15-Acetyldeoxynivalenol, 3-Acetyldeoxynivalenol, Fusarenon X, and Nivalenol

Neuroendocrine Peptides of the Gut and Their Role in the Regulation of Food Intake

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