ArticlePsychopharmacology2005
Targeted invalidation of CCK2 receptor gene induces anxiolytic-like action in light-dark exploration, but not in fear conditioning test.
Article in Psychopharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Effect of Benzodiazepines and Z-Drug Medications During Antenatal and Postnatal Depression and Anxiety: A Systematic Review and Meta-Analysis.Combinatorial chemistry & high throughput screening · 2025Pooled it
- Cholecystokinin/sulfakinin peptide signaling: conserved roles at the intersection between feeding, mating and aggression.Cellular and molecular life sciences : CMLS · 2022Review
- Cholecystokinin-Mediated Neuromodulation of Anxiety and Schizophrenia: A "Dimmer-Switch" Hypothesis.Current neuropharmacology · 2021Review
- Gender-Specific Association between Alcohol Consumption and Stress Perception, Depressed Mood, and Suicidal Ideation: The 2010-2015 KNHANES.Psychiatry investigation · 2019Article
- Conditioned stimulus presentations alter anxiety level in fear-conditioned mice.Molecular brain · 2019Article
- Interaction between the cholecystokinin and endogenous cannabinoid systems in cued fear expression and extinction retention.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
- Comparative density of CCK- and PV-GABA cells within the cortex and hippocampus.Frontiers in neuroanatomy · 2015Article
- Cholecystokinin-Like Peptide (DSK) in Drosophila, Not Only for Satiety Signaling.Frontiers in endocrinology · 2014Article
- Neuropeptide regulation of fear and anxiety: Implications of cholecystokinin, endogenous opioids, and neuropeptide Y.Physiology & behavior · 2012Review
- Cholecystokinin knock-down in the basolateral amygdala has anxiolytic and antidepressant-like effects in mice.Neuroscience · 2012Article
- GABAA receptor signaling in caudal periaqueductal gray regulates maternal aggression and maternal care in mice.Behavioural brain research · 2010Article
- Sex difference in alcoholism: who is at a greater risk for development of alcoholic complication?Life sciences · 2010Review
- GABA(A) receptor signaling in the lateral septum regulates maternal aggression in mice.Behavioral neuroscience · 2009Article
- Chronic stimulation of corticotropin-releasing factor receptor 1 enhances the anxiogenic response of the cholecystokinin system.Molecular psychiatry · 2009Article
- Importance of gastrin in the pathogenesis and treatment of gastric tumors.World journal of gastroenterology · 2009Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleEvidence suggests that gamma-aminobutyric acid (GABA) and cholecystokinin (CCK) have opposite roles in the regulation of anxiety.
objectivesThe aim of our work was to study the behaviour of CCK(2) receptor deficient mice in light-dark exploration and fear conditioning tests. Moreover, the action of diazepam and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), having the opposite effect on GABA(A) receptors, was evaluated on the exploratory behaviour in these mice. Expression levels of GABA(A) receptor subunit genes were also measured.
methodsLight-dark exploration and fear conditioning tests were used to determine changes in anxiety of mice. The action of diazepam (0.5-2 mg/kg i.p.) and DMCM (0.25-1 mg/kg i.p.) was studied in the light-dark box. The effect of DMCM was also evaluated in the motor activity test to demonstrate that its anti-exploratory action was not related to motor suppression. Expression levels of GABA(A) receptor subunit genes were determined by means of real-time polymerase chain reaction (qRT-PCR).
resultsFemale mice lacking CCK(2) receptors displayed increased exploratory activity in the light-dark box compared to their wild-type (+/+) littermates. Locomotor activity in the motility boxes and the intensity of freezing did not differ in wild-type (+/+) and homozygous (-/-) mice. Treatment with diazepam (0.5 mg/kg) increased the number of transitions in wild-type (+/+) animals, whereas in homozygous (-/-) mice diazepam (0.5-2 mg/kg) reduced exploratory activity. Administration of DMCM (0.25-1 mg/kg) induced an anxiogenic-like effect in homozygous (-/-) mice, but did not change their locomotor activity. Gene expression analysis established a 1.6-fold increase in the expression of the alpha2 subunit of GABA(A) receptors in the frontal cortex of homozygous (-/-) mice.
conclusionGenetic invalidation of CCK(2) receptors induced an anxiolytic-like action in exploratory, but not in conditioned models of anxiety. The observed reduction in anxiety in homozygous (-/-) mice is probably related to an increased function of GABAergic system in the brain.
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