Social interaction and social withdrawal in rodents as readouts for investigating the negative symptoms of schizophrenia

Abstract

Negative symptoms (e.g., asociality and anhedonia) are a distinct symptomatic domain that has been found to significantly affect the quality of life in patients diagnosed with schizophrenia. Additionally, the primary negative symptom of asociality (i.e., withdrawal from social contact that derives from indifference or lack of desire to have social contact) is a major contributor to poor psychosocial functioning and has been found to play an important role in the course of the disorder. Nonetheless, the pathophysiology underlying these symptoms is unknown and currently available treatment options (e.g., antipsychotics and cognitive-behavioral therapy) fail to reliably produce efficacious benefits. Utilizing rodent paradigms that measure social behaviors (e.g., social withdrawal) to elucidate the neurobiological substrates that underlie social dysfunction and to identify novel therapeutic targets may be highly informative and useful to understand more about the negative symptoms of schizophrenia. Accordingly, the purpose of this review is to provide an overview of the behavioral tasks for assessing social functioning that may be translationally relevant for investigating negative symptoms associated with schizophrenia.

Anxiety does not contribute to social withdrawal in the subchronic phencyclidine rat model of schizophrenia

“…Although we performed the social interaction test under non-anxiogenic conditions (Wilson and Koenig, 2014), the lack of pro-social effect of diazepam in control animals (Fig. 2C) might appear surprising (Costall et al, 1991; File and Seth, 2003).…”

“…by habituating animals to the arena and changing light conditions) to minimize the contribution of anxiety to the behavioral outcomes (Wilson and Koenig, 2014). Nevertheless, even under non-anxiogenic conditions, we cannot rule out that anxiety might still contribute to social withdrawal.…”

Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders

“…Hence, efforts are being made to improve its study in rodent models, though this remains a difficult task. Most work has focussed on social recognition, and various ways 30 of manipulating social interaction, itself a complex construct (Millan and Bales, 2013;Wilson and Koenig, 2014). In fact, fully-fledged social cognition (theory of mind and emotional processing) is probably not present in rodents underpinning the quest for alternative species for its study (Brune et al, 2006;Millan et al, 2012).…”

Schizophrenia and Social Cognition: A Review of Concepts and Treatment Options

“…[7,24]. Cognitive appraisal, which is the mean human beings use subconsciously to regulate emotions before expressing them, in order to deliver a reaction of adequate level, has been observed to be less frequently used by schizophrenic patients [2,19].…”

“…Experimental models have shown that psychotic subjects seek social withdrawal, which is associated with altered neural pathways and receptors [5,9,16,17]. Patients with schizophrenia often find themselves being unable to recognize facial expressions or misunderstanding comments, even having trouble assessing whether someone is addressing them or not, and they progressively become socially isolated [2,18,19]. As such, social impairment has a stronger impact on quality of life than non-social impairment [2,20].…”