ArticlePsychopharmacology2003
Targeted mutation of CCK2 receptor gene modifies the behavioural effects of diazepam in female mice.
Article in Psychopharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Gender-Specific Association between Alcohol Consumption and Stress Perception, Depressed Mood, and Suicidal Ideation: The 2010-2015 KNHANES.Psychiatry investigation · 2019Article
- Control of Food Intake by Gastrointestinal Peptides: Mechanisms of Action and Possible Modulation in the Treatment of Obesity.Journal of neurogastroenterology and motility · 2017Review
- Co-administration of subeffective anxiolytic doses of diazepam and hydroxyzine in elevated zero-maze in mice.Psychiatry investigation · 2011Article
- Sex difference in alcoholism: who is at a greater risk for development of alcoholic complication?Life sciences · 2010Review
- Wiring and volume transmission in rat amygdala. Implications for fear and anxiety.Neurochemical research · 2008Article
- Targeted invalidation of CCK2 receptor gene induces anxiolytic-like action in light-dark exploration, but not in fear conditioning test.Psychopharmacology · 2005Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
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Abstract
rationaleEvidence suggests that GABA and CCK have opposite roles in the regulation of anxiety.
objectiveThe aim of the present work was to study diazepam-induced anxiolytic-like action and impairment of motor co-ordination, and the parameters of benzodiazepine receptors in mice lacking CCK2 receptors.
methodsThe action of diazepam (0.5-3 mg/kg i.p.) was studied in the elevated plus-maze model of anxiety and rotarod test using mice lacking CCK2 receptors. The parameters of benzodiazepine receptors were analysed using [3H]-flunitrazepam binding.
resultsIn the plus-maze test, the exploratory activity of the homozygous (-/-) mice was significantly higher compared to their wild-type (+/+) littermates. However, the wild-type (+/+) mice displayed higher sensitivity to the anxiolytic-like action of diazepam. Even the lowest dose of diazepam (0.5 mg/kg) induced a significant increase of open arm entries in the wild-type (+/+) mice. A similar effect in the homozygous (-/-) mice was established after the administration of diazepam 1 mg/kg. The highest dose of diazepam (3 mg/kg) caused a prominent anxiolytic-like effect in the wild-type (+/+) mice, whereas in the homozygous (-/-) animals suppression of locomotor activity was evident. The performance of the homozygous (-/-) mice in the rotarod test did not differ from that of the wild-type (+/+) littermates. However, a difference between the wild-type (+/+) and homozygous (-/-) animals became evident after treatment with diazepam. Diazepam (0.5 and 3 mg/kg) induced significantly stronger impairment of motor co-ordination in the homozygous (-/-) mice compared to their wild-type (+/+) littermates. The density of benzodiazepine binding sites was increased in the cerebellum, but not in the cerebral cortex and hippocampus, of the homozygous (-/-) mice.
conclusionsFemale mice lacking CCK2 receptors are less anxious than their wild-type (+/+) littermates. The reduced anxiety in homozygous (-/-) mice probably explains why the administration of a higher dose of diazepam is necessary to induce an anxiolytic-like action in these animals. The highest dose of diazepam (3 mg/kg) induced significantly stronger suppression of locomotor activity and impairment of motor co-ordination in the homozygous (-/-) mice compared to the wild-type (+/+) littermates. The increase in the action of diazepam is probably related to the elevated density of benzodiazepine receptors in the cerebellum of homozygous (-/-) mice. The present study seems to be in favour of increased tone of the GABAergic system in mice without CCK2 receptors.
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