Neuropeptide modulation of social and exploratory behaviors in laboratory rodents

Crawley, Jacqueline N.; Hays, Sally E.; O’Donohue, Thomas L.; Paul, Steven M.; Goodwin, F. K.

doi:10.1016/0196-9781(81)90066-8

Cited by 60 publications

(12 citation statements)

References 24 publications

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“…CCK receptors are distributed in many areas of the brain, including the frontal cortex, hippocampus, nucleus tractus solitarius (NTS), and the hypothalamus, areas associated with behaviors, including ingestion, memory, and anxiety (2,6,36,52), and three forms of CCK (CCK-4, CCK-8, and CCK-33) interact with these brain CCK receptors (40,45,50,65). Intraventricular or intravenous administration of CCK-8 modulates exploratory behavior and memory, and rats lacking functional CCK1 receptors have impaired learning and memory (8,45). These observations collectively imply that endogenous CCK is a major controller of many behaviors and especially of cognitive function and food intake.…”

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confidence: 78%

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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confidence: 78%

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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“…The peripheral administration of CCK produces many other effects upon the central nervous system in addition to those on satiety and feeding. One is a decrease in exploratory behaviour, in which the vagus nerve also plays an important role (Crawley et al, 1981a; but see Crawley et al, 1081b). Futhermore, CCK is able to cause sedation (Itoh and Katsuura, 1981;Zetler, 19811, ptosis (Zetler, 19801, and analgesia (Jurna and Zetler, 1981;Zetler, 1980; but see Faris et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

On the distribution of cholecystokinin receptor binding sites in the human brain: An autoradiographic study

Dietl¹,

Probst²,

Palacios³

1987

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Cholecystokinin (CCK) binding sites were localized by in vitro autoradiography in human postmortem brain materials from 12 patients without reported neurological diseases using [125I]Bolton-Hunter CCK octapeptide (BHCCK-8) as a ligand. The pharmacological characteristics of BHCCK-8 binding to mounted tissue sections were comparable to those previously reported in the rat. CCK-8 being the most potent displacer, followed by caerulein, CCK-4, and gastrin I. The distribution of BHCCK-8 binding sites was heterogeneous. These sites were highly concentrated in a limited number of gray matter areas and nuclei. The highest binding densities were seen in the glomerular and external plexiform layers of the olfactory bulb. BHCCK-8 binding sites were also enriched in the neocortex, where they presented a laminar distribution with low levels in lamina I, moderate concentration in laminae II to IV, high density in lamina V, and low levels in lamina VI. A different laminar distribution was seen in the visual cortex, where a low receptor density was observed in lamina IV but higher density in laminae II and VI. In the basal ganglia the nucleus accumbens, caudatus, and the putamen presented moderate to high densities of binding sites, while the globus pallidus lacked sites of BHCCK-8 binding. In the limbic system the only area presenting moderate to high density was the amygdaloid complex, particularly in the granular nucleus, while most of the thalamic nuclei were extremely poor or lacked BHCCK-8 binding. The hippocampal formation showed low (CA1-3) to moderate (subiculum) densities. Midbrain areas generally disclosed very low levels of BHCCK-8 binding sites. The pontine gray and the nucleus reticularis tegmenti pontis showed a relatively high density of CCK-8 receptor specific binding. Moderate to very high densities were found in few nuclei of the lower brainstem and spinal cord as the inferior olives and their accessory nuclei, the arcuate nuclei, the striae medullares, the efferent (motor) nucleus of the vagus, and the substantia gelatinosa of the cervical and thoracic spinal cord. These results are discussed in relation to the distribution of endogenous peptide and to the known physiological and pharmacological effects of substances acting on these receptors.

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“…The lack of effect following systemic administration of pentagastrin indicates a central mechanism of action for this compound. It is known that peripheral administration of CCK receptor agonists can impair motor activity (Crawley et al, 1981) and this could complicate interpretation of the effect on anxiety. However, in the present study the anxiogenic-like effect of pentagastrin occurred at doses that failed to produce sedation in mice or affect spontaneous locomotor activity in the rat elevated X-maze.…”

Section: Discussionmentioning

confidence: 99%

The behavioural properties of CI‐988, a selective cholecystokinin_B receptor antagonist

Singh¹,

Field²,

Hughes³

et al. 1991

British J Pharmacology

136

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1 The behavioural effects of a selective cholecystokininB (CCKB) receptor antagonist CI-988 were investigated in rodents. 2 In three rodent tests of anxiety (rat elevated X-maze, rat social interaction test and mouse light/dark box) CI-988 over the dose range 0.001-I0.Omgkg 1, (i.p.) produced an anxiolytic-like action. The magnitude of this effect was similar to that of chlordiazepoxide (CDP). In contrast, the selective CCKA receptor antagonist, devazepide, was inactive. CI-988 also showed anxiolytic-like action in the rat conflict test but the magnitude of this effect was about 2.5 fold less than that of CDP. 3 Central but not peripheral administration of the selective CCKB receptor agonist, pentagastrin, like FG 7142, produced an anxiogenic-like action. 4 The pentagastrin-induced anxiety was dose-dependently antagonized by CI-988, whereas devazepide was inactive. However, ten times higher doses of CI-988 were required to block a similar action of FG 7142. 5 In contrast to CDP, CI-988 up to 3000 fold higher doses than those inducing anxiolysis was inactive in tests measuring sedation and ataxia. It also failed to antagonize pentylenetetrazol-induced tonic seizures. Furthermore, CI-988 did not interact with alcohol or barbiturates. Thus, CI-988 appears to be an anxioselective compound. 6 The anxiolytic-like action of CDP in the rat elevated X-maze was dose-dependently antagonized by flumazenil. In contrast, the benzodiazepine receptor antagonist failed to block a similar effect of Thus, CI-988 shows anxiolytic-like activity in several animal models of anxiety. The anxiolytic-like effect of CI-988 involves a novel mechanism of action, that is likely to be mediated by selective antagonism of the brain CCKB receptor. It is suggested that CI-988 should have a better side-effect profile in man than the benzodiazepines.

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Neuropeptide modulation of social and exploratory behaviors in laboratory rodents

Cited by 60 publications

References 24 publications

Characterization of mice lacking the gene for cholecystokinin

Characterization of mice lacking the gene for cholecystokinin

On the distribution of cholecystokinin receptor binding sites in the human brain: An autoradiographic study

The behavioural properties of CI‐988, a selective cholecystokinin_B receptor antagonist

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Neuropeptide modulation of social and exploratory behaviors in laboratory rodents

Cited by 60 publications

References 24 publications

Characterization of mice lacking the gene for cholecystokinin

Characterization of mice lacking the gene for cholecystokinin

On the distribution of cholecystokinin receptor binding sites in the human brain: An autoradiographic study

The behavioural properties of CI‐988, a selective cholecystokininB receptor antagonist

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The behavioural properties of CI‐988, a selective cholecystokinin_B receptor antagonist