The need for guidance in antidepressant drug development: Revisiting the role of the forced swim test and tail suspension test.

Depressive disorders are one of the most common mental disorders globally and progress in treating these disorders has been hampered, in part, by a lack of suitable nonclinical efficacy tests. Two common tests used in nonclinical efficacy studies of antidepressants-the forced swim test (FST) and tail suspension test (TST)-have come under criticism in recent years for their inconsistency and lack of validity, yet they continue to be used in the pharmaceutical industry. In this review, we provide a rationale for why international pharmaceutical regulatory and guidance agencies should begin issuing direction on methods for non-clinical efficacy testing that traditionally use the FST and TST, particularly considering that some regulators, such as those in the U.S. and E.U., allow the authorization of clinical trials to proceed without requiring tests in animals. The area of antidepressant drug discovery represents an important opportunity for reducing the attrition of psychiatric drugs, harmonizing regulatory requirements, and reducing animal use. Specific recommendations for the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) have been provided.

Developing a Collaborative Agenda for Humanities and Social Scientific Research on Laboratory Animal Science and Welfare.

Improving laboratory animal science and welfare requires both new scientific research and insights from research in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the '3Rs'), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they design research programmes, generate results, engage users, and seek to influence policy in different ways. To facilitate dialogue and future research at this interface, we convened an interdisciplinary group of 45 life scientists, social scientists, humanities scholars, non-governmental organisations and policy-makers to generate a collaborative research agenda. This drew on methods employed by other agenda-setting exercises in science policy, using a collaborative and deliberative approach for the identification of research priorities. Participants were recruited from across the community, invited to submit research questions and vote on their priorities. They then met at an interactive workshop in the UK, discussed all 136 questions submitted, and collectively defined the 30 most important issues for the group. The output is a collaborative future agenda for research in the humanities and social sciences on laboratory animal science and welfare. The questions indicate a demand for new research in the humanities and social sciences to inform emerging discussions and priorities on the governance and practice of laboratory animal research, including on issues around: international harmonisation, openness and public engagement, 'cultures of care', harm-benefit analysis and the future of the 3Rs. The process outlined below underlines the value of interdisciplinary exchange for improving communication across different research cultures and identifies ways of enhancing the effectiveness of future research at the interface between the humanities, social sciences, science and science policy.

Behavioural responses of Eastern grey squirrels, Sciurus carolinensis, to cues of risk while foraging.

Previous studies have shown that Eastern grey squirrels modify their behaviour while foraging to offset risks of social and predatory costs, but none have simultaneously compared whether such modifications are performed at a cost to foraging. The present study directly compares how grey squirrels respond to cues of these risks while foraging. We simulated social risk and predatory risk using acoustic playbacks of stimuli that grey squirrels might be exposed to at a foraging patch: calls of conspecifics, heterospecifics (competitor and non-competitor) and predators. We found that grey squirrels responded to predator, heterospecific competitor and conspecific playbacks by altering their foraging and vigilance behaviours. Foraging was most disrupted by increased vigilance when we played calls of predators. Squirrels' response to calls of heterospecific competitors did not differ from their response to conspecific calls, and they resumed foraging more quickly after both compared to predator calls: whereas they showed little response to calls of non-competitor heterospecifics and a white noise control. We conclude that squirrels respond differentially to calls made by conspecifics, heterospecific competitors and predators, with the most pronounced response being to calls of predators. We suggest that squirrels may view conspecific and corvid vocalisations as cues of potential conflict while foraging, necessitating increased vigilance.