Impaired Learning and Memory in OLETF Rats Without Cholecystokinin (CCK)-A Receptor

Nomoto, Shigeki; Miyake, Miho; Ohta, Minoru; Funakoshi, Akihiro; Miyasaka, Kyoko

doi:10.1016/s0031-9384(99)00033-5

Cited by 47 publications

(24 citation statements)

References 28 publications

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“…The present findings together with further DA-related deficits described earlier in the OLETF rats (e.g., learning, memory, motor, and sensory-motor gating deficits [9,17,21,35]) and with the suggested role of CCK in behavioral sensitization to psychostimulants [8] supports the notion that altered sweet preference and overall augmented ingestive responses may represent a component of a more generalized increase in sensitivity of the reward system in this obese rat model.…”

Section: Potential Mechanismssupporting

confidence: 89%

Altered dopamine D2 receptor function and binding in obese OLETF rat

Hajnal

Margas

Covașă

2008

Brain Research Bulletin

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A decrease in D2 -like receptor (D2R) binding in the striatum has been reported in obese individuals and drug addicts. Although natural and drug rewards share neural substrates, it is not clear whether such effects contribute also to overeating on palatable meals as an antecedent of dietary obesity. Therefore, we investigated receptor density and the effect of the D2R agonist quinpirole (0.05, 0.5 mg/kg, S.C.) on locomotor activity and sucrose intake in a rat model of diet-induced obesity, the CCK-1 receptor-deficient Otsuka Long Evans Tokushima Fatty (OLETF) rat. Compared to agematched lean controls (LETO), OLETF rats expressed significantly lower [125I]-iodosulpride binding in the accumbens shell (−16%, p<0.02). Whereas the high dose of quinpirole increased motor activity in both strains equally, the low dose reduced activity more in OLETF. Both doses significantly reduced sucrose intake in OLETF but not LETO. These findings demonstrate an altered D2R signaling in obese OLETF rats similar to drug-induced sensitization and suggest a link between this effect and avidity for sucrose in this model.

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Section: Potential Mechanismssupporting

confidence: 89%

Altered dopamine D2 receptor function and binding in obese OLETF rat

Hajnal

Margas

Covașă

2008

Brain Research Bulletin

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“…LETO pups exhibited a pronounced decrease in their latency to start feeding compared with their OLETF controls, which might suggest better learning or memory skills. It was previously established that adult OLETF rats have impaired learning and memory compared with their LETO controls (50). Another way of explaining this is that OLETF rats expressed the quickest response to food at the younger age, whereas LETO pups were able to demonstrate this ability only in a later stage/developmental age.…”

Section: Discussionmentioning

confidence: 98%

Independent ingestion and microstructure of feeding patterns in infant rats lacking CCK-1 receptors

Blumberg

Haba²,

Schroêder³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Otsuka Long-Evans Tokushima fatty (OLETF) rats are a strain of Long-Evans Tokushima Otsuka (LETO) rats that do not express CCK-1 receptors, developing in adulthood, hyperphagia, obesity, and non-insulin-dependent diabetes mellitus (NIDDM). We examined weight gain and meal patterns during a 30-min independent ingestion test on postnatal days 2-4 and again on days 9 -11 in OLETF and LETO rat pups. OLETF pups were significantly heavier compared with their LETO controls at both ages, and they consumed significantly more of the sweet milk diet. The difference in intake can be attributed to a significant increase in meal size and duration. Number of clusters and bursts of licking within a meal were greater in OLETF rat pups, with no difference between strains in burst and cluster size. Interlick interval (ILI) was not significantly different between OLETF and LETO pups. This measure decreased on days 9 -11 compared with days 2-4 in both strains. Latency to start feeding was significantly shorter on days 2-4 in OLETF vs. LETO pups, but this difference disappeared at the second test at the older age. Two-to four-day-old OLETF pups consumed a larger volume of milk during the first minute of feeding, and their initial lick rate and decay of lick rate were significantly larger compared with their LETO controls. Lack of CCK-1 receptors, or other OLETF-related abnormalities, therefore, resulted in a satiation deficit, leading to increased meal size, hyperphagia, and increased weight gain as early as 2-4 postnatal days. cholecystokinin; obesity; independent ingestion; meal-patterns; Otsuka Long-Evans Tokushima fatty rats; infant rats THE BRAIN-GUT PEPTIDE CHOLECYSTOKININ (CCK) has been demonstrated to reduce food intake in a dose-related manner in different species and experimental designs (3,29,35). Entry of food into the intestine triggers the release of endogenous CCK by the intestinal mucosa, thereby activating CCK-1 receptors located in the periphery to transmit through the vagus nerve a neural signal to the brain, which subsequently terminates feeding and initiates the sequence of behaviors associated with satiety (4, 60).CCK was found to reduce meal size and duration (29, 38) and to induce an earlier appearance of behavioral satiety. The satiety produced by endogenous or exogenous administration of the peptide is mediated via interaction with CCK-1 receptors rather than CCK-2 receptors (5, 44). CCK-1 receptors are abundant in peripheral organs and in a few discrete brain regions (33, 45).Exogenous and endogenous CCK, through receptors of CCK-1, have been shown to reduce feeding in newborn and infant rats independently ingesting their first meal away from the dam (53, 61, 68). Furthermore, CCK-1 receptors appear to mediate a portion of the reduction of intake produced by a preload of corn oil (but not by mineral oil, glucose, 2-deoxy-D-glucose, maltose, or peptone) in infant rats (66 -69). These findings suggest that the CCK system can function selectively at a preweanling age, mediating the emerging feeding-regulatory ...

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“…Spatial memory involves several areas of the brain, and especially the amygdala and hippocampus (1,10,12,15,50,55,60). Further, these brain areas express CCK1/CCK2 receptors (72,74).…”

Section: Discussionmentioning

confidence: 99%

Characterization of mice lacking the gene for cholecystokinin

Samuelson²,

Chambers

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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acts peripherally as a satiating peptide released during meals in response to lipid feeding and centrally functions in the modulation of feeding, exploratory, and memory activities. The present study determined metabolic parameters, food intake, anxiety-like behaviors, and cognitive function in mice lacking the CCK gene. We studied intestinal fat absorption, body composition, and food intake of CCK knockout (CCK-KO) mice by using the noninvasive measurement of intestinal fat absorption along with quantitative magnetic resonance (QMR) imaging and the DietMax system, respectively. Additionally, exploratory and memory capacities were assessed by monitoring running wheel activity and conducting elevated plus-maze and Morris watermaze tests with these mice. Compared with wild-type (WT) littermate controls, CCK-KO mice had normal food intake, fat absorption, body weight, and body mass. CCK-KO mice ate more food than control animals during the light period and less food during the dark period. Energy expenditure was unchanged between the genotypes; however, CCK-KO mice displayed greater fatty acid oxidation. CCK-KO mice were as active as WT animals in the running wheel test. CCK-KO mice spent more time in the closed arms of an elevated plus-maze, indicative of increased anxiety. Additionally, CCK-KO mice exhibited attenuated performance in a passive avoidance task and impaired spatial memory in the Morris water maze test. We conclude that CCK is involved in metabolic rate and is important for memory and exploration. CCK is intimately involved in multiple processes related to cognitive function and food intake regulation. cholecystokinin 1 receptor; cholecystokinin 2 receptor; cognitive behaviors CCK OCCURS as a carboxyl terminally amidated peptide that exists in several possible lengths (43,58,66). In rats and mice, the predominant circulating forms include cholecystokinin octapeptide (CCK-8) and CCK-22, whereas larger molecular forms (CCK-33 and CCK-58) are also present in human and canine plasma (42,61,38,63,16). These molecular forms are processed from a 115-amino acid preprohormone product of the gene residing in chromosome 3 in rodents (13, 57). Intestinal endocrine cells secrete a mixture of medium-sized CCK forms, while central and peripheral neurons mainly release sulfated forms of 62). In response to consumption of either lipid and protein, CCK is produced and secreted by intestinal I cells (41). The release of CCK from neurons is caused by potassium ion-induced depolarization (15). Peripheral CCK is involved in modulating intestinal motility, stimulating pancreatic enzyme secretion, enhancing gallbladder contraction, and regulating meal size (11,21,24,29,48,56,64,69).CCK is also a neurotransmitter in many areas of the nervous system (6). Intraperitoneal or central administration of either purified CCK extracts or synthetic CCK-8 to fasted rats reduces food intake (22,33,37,54), and this is manifested by a reduction of meal size as opposed to reduced frequency of meals (22,37). Two types of CCK receptors (CCK1...

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Impaired Learning and Memory in OLETF Rats Without Cholecystokinin (CCK)-A Receptor

Cited by 47 publications

References 28 publications

Altered dopamine D2 receptor function and binding in obese OLETF rat

Altered dopamine D2 receptor function and binding in obese OLETF rat

Independent ingestion and microstructure of feeding patterns in infant rats lacking CCK-1 receptors

Characterization of mice lacking the gene for cholecystokinin

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