Do animal models of anxiety predict anxiolytic-like effects of antidepressants?

Abstract

Chronically administered antidepressant drugs, particularly selective serotonin (5-HT) reuptake inhibitors (SSRIs), are clinically effective in the treatment of all anxiety disorders, while the clinical effectiveness of "traditional" anxiolytics, such as benzodiazepines (BDZs), is limited to generalised anxiety disorder or acute panic attacks. This implies that animal models of anxiety should be sensitive to SSRIs and other antidepressants in order to have predictive validity. We reviewed the literature on the effects of antidepressants in the so-called animal models of anxiety and found that only the isolation-induced calls in guinea-pig pups may reveal anxiolytic-like action of all antidepressant classes after acute administration. Some other models, such as marble-burying or conditioned-freezing behaviours, and isolation- or shock-induced ultrasonic vocalisation models, may detect anxiolytic-like activity of acutely administered antidepressants, although the sensitivity of these models is usually limited to SSRIs and other drugs affecting 5-HT uptake. The predictive validity of models of "anxiety", such as the plus-maze and light-dark transition tests or stress-induced hyperthermia, appears to be limited to BDZ-related drugs. Far less work has been done on chronic administration of antidepressants in animal anxiety models. Unless and until such studies have been undertaken, the true predictive value of the anxiety models will remain unknown.

Anti-inflammatory agents attenuate the passive responses of guinea pig pups: Evidence for stress-induced sickness behavior during maternal separation

“…First, a reduction in active behavior is a commonly observed sickness response (Hart, 1988) and so an anti-inflammatory might be expected to oppose this effect and increase activity. Second, the vocalizing of guinea pig pups during isolation procedures is considered to reflect an anxiety-like state (Borsini, Podhorna, & Marazziti, 2002). Since α-MSH has been found to produce anxiogenic effects in some species (Panksepp & Abbott, 1990;Rao et al, 2003) there would be reason to expect α-MSH would increase vocalizing.…”

SB-649915-B, a Novel 5-HT1A/B Autoreceptor Antagonist and Serotonin Reuptake Inhibitor, is Anxiolytic and Displays Fast Onset Activity in the Rat High Light Social Interaction Test

“…SSRIs have been shown to have acute behavioral effects in a number of preclinical assays of anxiety (for review, see Borsini et al, 2002). When rat pups are separated from their mothers they emit ultrasonic vocalizations which can be attenuated by acutely administered anxiolytic agents such as benzodiazepines and SSRIs (Gardner, 1985;Olivier et al, 1998).…”

Resolving the neural circuits of anxiety

“…They have a high degree of face validity, in that most of the anxiety disorders include a component of avoidance of a potentially hazardous stimulus. Furthermore, anxiety-like behaviors in these tasks are reduced by anxiolytic drugs, particularly BZDs 42 . Finally, limited training is required for animals to perform them, rendering this group of anxiety assays high throughput.…”