Pharmacological and methodological aspects of the separation-induced vocalization test in guinea pig pups; a systematic review and meta-analysis

Lucianne Groenink,P Monika Verdouw,Brenda Bakker,Kimberley E Wever

doi:10.1016/j.ejphar.2014.10.062

Abstract

The separation-induced vocalization test in guinea pig pups is one of many that has been used to screen for anxiolytic-like properties of drugs. The test is based on the cross-species phenomenon that infants emit distress calls when placed in social isolation.Here we report a systematic review and meta-analysis of pharmacological intervention in the separation-induced vocalization test in guinea pig pups. Electronic databases were searched for original research articles, yielding 32 studies that met inclusion criteria. We extracted data on pharmacological intervention, animal and methodological characteristics, and study quality indicators.Meta-analysis showed that the different drug classes in clinical use for the treatment of anxiety disorders, have comparable effects on vocalization behaviour, irrespective of their mechanism of action. Of the experimental drugs, nociception (NOP) receptor agonists proved very effective in this test. Analysis further indicated that the commonly used read-outs total number and total duration of vocalizations are equally valid. With regard to methodological characteristics, repeated testing of pups as well as selecting pups with moderate or high levels of vocalization were associated with larger treatment effects. Finally, reporting of study methodology, randomization and blinding was poor and Egger’s test for small study effects showed that publication bias likely occurred.This review illustrates the value of systematic reviews and meta-analyses in improving translational value and methodological aspects of animal models. It further shows the urgent need to implement existing publication guidelines to maximize the output and impact of experimental animal studies.

Highlights

In the search for novel pharmacological treatment of anxiety disorders, a wide range of animal models and tests has been used
In this systematic review and meta-analysis, we studied the effect of registered anxiolytics and antidepressants with anxiolytic properties in the separation-induced vocalization test in guinea pig pups, examined potential differences between these classes, and assessed the effect of experimental drug classes in this test
We found that selective serotonin re-uptake inhibitors (SSRIs), benzodiazepines and partial 5-HT1A receptor agonists all reduced vocalization behaviour to a similar extent

Summary

Introduction

In the search for novel pharmacological treatment of anxiety disorders, a wide range of animal models and tests has been used. Anxiety tests may either be performed in naïve animals or in animals in which aspects of the disease are modelled, e.g. by genetic modification or exposure to traumatizing stimuli. The read-outs quantified in the test itself may be based on innate anxiety, conditioned fear or conflict behaviour. Together with the still limited understanding of the pathophysiology of anxiety disorders, this lack of knowledge may have hampered the translation of preclinical findings to the clinic (see Griebel and Holmes, 2013). Limitations in n Correspondence to: Division of Pharmacology, Department of Pharmaceutical Sciences, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.

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