Comparison of Buspirone and Diazepam in Generalized Anxiety Disorder

Griebel

European Journal of Pharmacology

2003

258

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 Batterysupporting

confidence: 58%

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

Griebel

European Journal of Pharmacology

2003

258

159

“…This delayed onset of action of buspirone has previously been noted in several studies [Feighner et al, 1982: Wheatley, 1982: Tyrer and Owen, 1984Tyrer et al. 1985;Jacobson et al. 1985: Pecknold etal., 1985: Rickels et al.…”

Section: Discussionmentioning

confidence: 84%

Controlled Comparison of Buspirone and Oxazepam in Generalized Anxiety

et al. 1990

The anxiolytic activity, the tolerance, and the withdrawal symptoms of buspirone and oxazepam were compared in two groups of 14 and 12 outpatients, respectively, suffering from generalized anxiety in a double-blind study with random allocation of patients. The 6-week active period was preceded and followed by 1 and 2 weeks on placebo, respectively. Clinical assessments were performed before and after the predrug placebo period and every 2 weeks thereafter and included Hamilton anxiety and depression scales and AMDP anxiety subscale. The initial daily dose was 15 mg buspirone or 45 mg oxazepam in 3 intakes and the mean final daily doses were 22.2 and 55.8 mg, respectively. Results showed a slower anxiolytic activity of buspirone compared to oxazepam with less improvement after 2 weeks of treatment. The rebound anxiety following abrupt discontinuation of the drug and the level of side effects did not significantly differ between the two compounds.

“…In human beings, however, acute administration is not anxiolytic, and in a non-human primate model, does not reduce phasic fear (Winslow et al, 2007). For clinical anxiolysis, chronic administration is required (Jacobson et al, 1985;Goa and Ward, 1986;Goodman, 2004), suggesting that the mechanism of action for effects on phasic startle potentiation in rats (which may not involve serotoninFDavis et al (1988)) and for clinical efficacy in human beings may be different. In Experiment 4, we replicated the frequently reported effect observed in rats and, in Experiment 5, observed a quantitatively similar difference.…”

Section: Discussionmentioning

confidence: 99%

Phasic and Sustained Fear are Pharmacologically Dissociable in Rats

Miles

Davis

Walker

2011

Neuropsychopharmacol

Previous findings suggest differences in the neuroanatomical substrates of short-(seconds) vs longer-duration (minutes) fear responses. We now report that phasic and sustained fear can also be differentiated pharmacologically, based on their response to several treatments that either are or are not clinically effective anxiolytics. For these experiments, short-or long-duration clicker stimuli were paired with footshock. Acoustic startle amplitude was later measured in the absence of the clicker, or within seconds (phasic fear) or minutes (sustained fear) of its onset. Before testing, rats received a single injection of vehicle, the benzodiazepine chlordiazepoxide, the 5HT 1A agonist and dopamine D2 antagonist buspirone, the selective serotonin reuptake inhibitor fluoxetine, or a 3-week treatment with either vehicle or fluoxetine. Chlordiazepoxide blocked sustained, but not phasic startle increases. Acute buspirone, which is not anxiolytic in human beings, did not affect sustained startle increases, but did disrupt phasic increases. Chronic fluoxetine blocked sustained startle increases and unreliably reduced phasic increases; acute fluoxetine affected neither. The results indicate that phasic and sustained fear responses can be pharmacologically dissociated, further validating this distinction, and suggest that sustained startle increases may be especially useful as anxiety models and anxiolytic screens.