Current pharmacological models of social withdrawal in rats

Abstract

Social dysfunction in schizophrenia is one of the core negative symptoms, which to date is not adequately addressed by treatment with both typical and atypical antipsychotics. A number of different pharmacological models of social withdrawal are used to mimic social dysfunction in rats, such as amphetamine, N-methyl-D-aspartic acid antagonists, cannabinergic and serotonergic receptor ligands. The purpose of this review is to discuss and compare these models of social withdrawal with a focus on their face, construct and predictive validities. Various techniques and strategies used to observe and analyze rodent social behaviour and other factors that are of relevance to this paradigm have also been examined. After comparing the reports, we are of the opinion that to improve replicability of any given model and its antipsychotic screening potential and the reliability of comparisons made, efforts need to be directed towards cross-laboratory standardization of variables that may confound experimental outcomes and cause discrepancies in results reported. In keeping with an earlier suggestion this may be facilitated through the creation of an online consortium for behavioural neuroscientists to share and compare methodologies, laboratory layouts and perhaps even raw data.

Phencyclidine-Induced Social Withdrawal Results from Deficient Stimulation of Cannabinoid CB1 Receptors: Implications for Schizophrenia

“…Also, PCP-treated rats represent the best pharmacological model of social withdrawal (negative symptom) in term of construct, face, and predictive validity (Gururajan et al, 2010). We previously showed that systemic administration of URB597, a drug that increases AEA levels by blocking its catabolic enzyme fattyacid amide hydrolase (FAAH), reverses PCP-induced social withdrawal (Seillier et al, 2010), thus strengthening the idea that cannabinoid compounds could attenuate negative symptoms.…”

Does cannabidiol have a role in the treatment of schizophrenia?

“…These include hyperactivity, social withdrawal (Gururajan et al, 2010) and disrupted PPI (Geyer et al, 2001). Using this MK-801 rodent model of aspects of schizophrenia, we evaluated the antipsychotic potential of CBD.…”

Towards the development of improved tests for negative symptoms of schizophrenia in a validated animal model

“…Carefully validated animal models combined with appropriate tests for negative symptoms in animals form a critical part of the development of new therapeutic strategies for negative symptoms (Barnes et al, 2014a;Neill et al, 2014). However, many aspects of negative symptom domains have been poorly investigated in animal studies and when they have, the most successful work has been conducted on the social withdrawal domain in rats (Gururajan et al, 2010;Moser, 2014;Neill et al, 2010Neill et al, , 2014Wilson and Koenig, 2014). These studies are certainly valuable and of ethological relevance in such a gregarious species.…”