title: Pharmacological and methodological aspects of the separation-induced vocalization test in guinea pig pups; a systematic review and meta-analysis.
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.
authors.affiliation: Pharmacology, Utrecht Institute of Pharmaceutical Sciences (UIPS), Brain Center Rudolf Magnus (BCRM), Utrecht, The Netherlands. Electronic address: l.groenink@uu.nl.
authors.forename: Lucianne
authors.initials: L
authors.lastname: Groenink
authors.affiliation: Pharmacology, Utrecht Institute of Pharmaceutical Sciences (UIPS), Brain Center Rudolf Magnus (BCRM), Utrecht, The Netherlands.
authors.forename: P Monika
authors.initials: PM
authors.lastname: Verdouw
authors.affiliation: Pharmacology, Utrecht Institute of Pharmaceutical Sciences (UIPS), Brain Center Rudolf Magnus (BCRM), Utrecht, The Netherlands.
authors.forename: Brenda
authors.initials: B
authors.lastname: Bakker
authors.affiliation: SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE), Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Kimberley E
authors.initials: KE
authors.lastname: Wever
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D012934:Social Isolation / Q000523:psychology*; D014828:Vocalization, Animal / Q000187:drug effects*
chemical_list: D014151:Anti-Anxiety Agents
keywords: Animal model; Anxiety; Anxiolytic; Drug effects; Guinea pig; Vocalization Review