High- and Low-conditioned Behavioral effects of midazolam in Carioca high- and low-conditioned freezing rats in an ethologically based test

•CHF and CLF rats are two bidirectional lines that are based on contextual fear conditioning.•CHF rats have a more “anxious” phenotype than CLF rats in the EPM.•Intraperitoneal injections of midazolam had anxiolytic behavioral effects in CHF and CLF rats.•This pharmacological effect depends on genet...

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Veröffentlicht in:Neuroscience letters Jg. 715; S. 134632
Hauptverfasser: Cavaliere, Daniele Rodrigues, Maisonnette, Silvia, Krahe, Thomas E., Landeira-Fernandez, J., Cruz, Antonio Pedro Mello
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Ireland Elsevier B.V 10.01.2020
Schlagworte:
Animal models of anxiety
Animals
Anti-Anxiety Agents - pharmacology
Carioca high- and low-freezing rats
Conditioning, Classical - drug effects
Dose-Response Relationship, Drug
Immobility Response, Tonic - drug effects
Maze Learning
Midazolam
Midazolam - pharmacology
Phenotype
Rats, Inbred Strains
Selective Breeding
State and trait anxiety
Carioca high- and low-freezing rats
Midazolam
Animal models of anxiety
Selective breeding
State and trait anxiety
ISSN:0304-3940, 1872-7972, 1872-7972
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Zusammenfassung:•CHF and CLF rats are two bidirectional lines that are based on contextual fear conditioning.•CHF rats have a more “anxious” phenotype than CLF rats in the EPM.•Intraperitoneal injections of midazolam had anxiolytic behavioral effects in CHF and CLF rats.•This pharmacological effect depends on genetic variability associated with basal reactions to threatening situations.•The CHF and CLF breeding lines represent a useful genetic model for studying anxiety. The selective breeding of laboratory rodents with different anxiety-related traits is the subject of growing interest. The present study compared the effects of the benzodiazepine midazolam in the elevated plus maze (EPM) test of anxiety in two lines of Wistar rats that were selectively bred in our laboratory for either high or low anxiety-like traits based on a contextual freezing conditioning paradigm. After phenotyping anxiety-like traits (i.e., conditioned freezing behavior), Carioca High-Freezing [CHF], Carioca Low-Freezing [CLF]) and control rats were intraperitoneally injected (1.0 ml/kg) with .9 % saline or midazolam (.25, .5, .75, and 1.0 mg/kg) and subjected to the EPM 30 min later. After the saline injection, the CHF and CLF groups exhibited lower and higher open-arm exploration in the EPM, respectively, compared with control rats. These results indicate that anxiety-related traits previously selected from an associative learning paradigm can also be phenotypically expressed in an ethologically based animal model of anxiety. All midazolam doses significantly increased open-arm exploration in both CHF and control animals, but this anxiolytic-like effect in CLF rats was only observed at the lowest dose tested (.25 mg/kg). The present findings indicate that these two breeding lines of rats are a useful model for studying anxiety, and the anxiolytic effect of midazolam depends on genetic variability that is associated with basal reactions to threatening situations.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0304-3940
1872-7972
1872-7972
DOI:10.1016/j.neulet.2019.134632