Representation-mediated Aversion as a Model to Study Psychotic-like States in Mice

Background

The presence of positive symptoms, such as delusions or hallucinations, is a key feature of a psychotic-like state (American Psychiatric Association, 2000 and 2013; Tandon, 2013) and represents a major challenge to rodent models (Wong and Van Tol, 2003; van den Buuse et al., 2005; Mouri et al., 2007; Jones et al., 2011). Indeed, these symptoms are often neglected due to the lack of suitable animal models (Jones et al., 2011; Rubino and Parolaro, 2014 and 2016). Psychotogenic drug-induced hyperlocomotion in rodents has long been considered an acceptable approximation of positive symptoms of drug-induced psychotic-like states (Wong and Van Tol, 2003; van den Buuse et al., 2005; Mouri et al., 2007; Jones et al., 2011). However, locomotor activity cannot be used to study the mismatch between perception and reality that is the hallmark of positive psychotic-like states (Wong and Van Tol, 2003; van den Buuse et al., 2005). For instance, the ‘Diagnostic and Statistical Manual of Mental Disorders’ (DSM V) defines delusions as ‘erroneous beliefs that usually involve a misinterpretation of perception or experiences’ (American Psychiatric Association, 2013). To overcome this methodological limitation, recent studies have used behavioral procedures in rodents designed to measure the accuracy of mental representations of reality, also called ‘reality testing’ (McDannald and Schoenbaum, 2009; McDannald et al., 2011; Kim and Koh, 2016). Alterations in ‘reality testing’ performance can be an indication of an impairment in perception which, as we mentioned before, might lead to positive psychotic-like states such as delusions. Thus, we adapt these previous protocols (McDannald and Schoenbaum, 2009; McDannald et al., 2011; Wheeler et al., 2013; Kim and Koh, 2016) to design a behavioral paradigm for measuring ‘reality testing’ in mice (Busquets-Garcia et al., 2017). Notably, deficits in task performance induced by psychotogenic drugs (e.g., amphetamine or cannabinoids) seem to reflect the kind of perceptual alterations that are the hallmarks and early features of positive psychotic-like symptoms.