Diazepam changes risk assessment in an anxiety/defense test battery

Griebel

European Journal of Pharmacology

2003

Self Cite

257

159

The Mouse Defense Test Battery was developed from tests of defensive behaviors in rats, reflecting earlier studies of both acute and chronic responses of laboratory and wild rodents to threatening stimuli and situations. It measures flight, freezing, defensive threat and attack, and risk assessment in response to an unconditioned predator stimulus, as well as pretest activity and postthreat (conditioned) defensiveness to the test context. Factor analyses of these indicate four factors relating to cognitive and emotional aspects of defense, flight, and defensiveness to the test context. In the Mouse Defense Test Battery, GABA A -benzodiazepine anxiolytics produce consistent reductions in defensive threat/attack and risk assessment, while panicolytic and panicogenic drugs selectively reduce and enhance, respectively, flight. Effects of GABA A -benzodiazepine, serotonin, and neuropeptide ligands in the Mouse Defense Test Battery are reviewed. This review suggests that the Mouse Defense Test Battery is a sensitive and appropriate tool for preclinical evaluation of drugs potentially effective against defense-related disorders such as anxiety and panic. D

Section: The Anxiety/defense Test Batterymentioning

confidence: 55%

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

Griebel

European Journal of Pharmacology

2003

Self Cite

257

159

“…The phenomenon is consistent with a reduced anxiety-like behavior (ie, increase center time) and increased locomotor exploration (ie, increase horizontal and vertical activities). It has been demonstrated that in exploration-based tests for anxiety-like behaviors, such as the light-dark exploration or emergence tests, animals with anxiety would rather spend more time in the dark compartment (Blanchard et al, 1990;File, 2001;Holmes et al, 2003b). In light-dark exploration tests, the GAT1 À/À mice showed more transitions between light and dark compartments and spent more time in the light compartment than GAT1 + / + mice.…”

Section: Discussionmentioning

confidence: 99%

Reduced Anxiety and Depression-Like Behaviors in Mice Lacking GABA Transporter Subtype 1

Liu

Cai

et al. 2006

Neuropsychopharmacol

117

g-Aminobutyric acid (GABA) transporter subtype 1 (GAT1), which transports extracellular GABA into presynaptic neurons, plays an important regulatory role in the function of GABAergic systems. However, the contributions of the GAT1 in regulating mental status are not fully understood. In this paper, we observed the behavioral alterations of GAT1 knockout (GAT1 À/À ) mice using several depressionand anxiety-related models (eg, the forced-swimming test and the tail-suspension test for testing depression-related behaviors; the openfield test, the dark-light exploration test, the emergence test, and the elevated plus maze (EPM) test for anxiety-related behaviors). Here we found that GAT1 À/À mice showed a lower level of depression-and anxiety-like behaviors in comparison to wild-type mice. Furthermore, GAT1 À/À mice exhibited measurable insensitivity to selected antidepressants and anxiolytics such as fluoxetine, amitriptyline, buspirone, diazepam, and tiagabine in the tail-suspension test and/or the EPM test. Moreover, the basal level of corticosterone was found to be significantly lower in GAT1 À/À mice. These results showed that the absence of GAT1 affects mental status through enhancing the GABAergic system, as well as modifying the serotonergic system and the hypothalamic-pituitary-adrenal (HPA) activity in mice.

“…In exploration-based tests for anxiety-like behavior, such as the light2dark exploration or emergence tests, it can be difficult to dissociate a strong anxiety-like phenotype from an impairment in exploratory locomotion per se, as both can manifest as an inhibition of exploratory locomotion (Blanchard et al, 1990;Crawley, 2000;File, 2001;Holmes, 2001;McNaughton and Gray, 2000). In this context, 5-HTT À/À mice were no different from +/+ controls on independent measures of locomotor activity (ie entries and rears in the protected closed arms) in the elevated plus maze, under baseline conditions.…”

Section: Discussionmentioning

confidence: 99%

Mice Lacking the Serotonin Transporter Exhibit 5-HT1A Receptor-Mediated Abnormalities in Tests for Anxiety-like Behavior

Holmes

Yang

Lesch

et al. 2003

Neuropsychopharmacol

284

203

The serotonin transporter (5-HTT) regulates serotonergic neurotransmission via clearance of extracellular serotonin. Abnormalities in 5-HTT expression or function are found in mood and anxiety disorders, and the 5-HTT is a major target for antidepressants and anxiolytics. The 5-HTT is further implicated in the pathophysiology of these disorders by evidence that genetic variation in the promoter region of the HTT (SLC6A4) is associated with individual differences in anxiety and neural responses to fear. To further evaluate the role of the 5-HTT in anxiety, we employed a mouse model in which the 5-HTT gene (htt) was constitutively inactivated. 5-HTT À/À mice were characterized for anxiety-related behaviors using a battery of tests (elevated plus maze, light2dark exploration test, emergence test, and open field test). Male and female 5-HTT À/À mice showed robust phenotypic abnormalities as compared to +/+ littermates, suggestive of increased anxiety-like behavior and inhibited exploratory locomotion. The selective 5-HT 1A receptor antagonist, WAY 100635 (0.05-0.3 mg/kg), produced a significant anxiolytic-like effect in the elevated plus maze in 5-HTT À/À mice, but not +/+ controls. The present findings demonstrate abnormal behavioral phenotypes in 5-HTT null mutant mice in tests for anxiety-like and exploratory behavior, and suggest a role for the 5-HT 1A receptor in mediating these abnormalities. 5-HTT null mutant mice provide a model to investigate the role of the 5-HTT in mood and anxiety disorders.