Academic journal article Cognitive, Affective and Behavioral Neuroscience

Isolation Rearing Effects on Probabilistic Learning and Cognitive Flexibility in Rats

Academic journal article Cognitive, Affective and Behavioral Neuroscience

Isolation Rearing Effects on Probabilistic Learning and Cognitive Flexibility in Rats

Article excerpt

Published online: 13 August 2013

© Psychonomic Society, Inc. 2013

Abstract Isolation rearing is a neurodevelopmental manipulation that produces neurochemical, structural, and behavioral alterations in rodents that in many ways are consistent with schizophrenia. Symptoms induced by isolation rearing that mirror clinically relevant aspects of schizophrenia, such as cognitive deficits, open up the possibility of testing putative therapeutics in isolation-reared animals prior to clinical development. We investigated what effect isolation rearing would have on cognitive flexibility, a cognitive function characteristically disrupted in schizophrenia. For this purpose, we assessed cognitive flexibility using between- and within-session probabilistic reversal-learning tasks based on clinical tests. Isolation-reared rats required more sessions, though not more task trials, to acquire criterion performance in the reversal phase of the task, and were slower to adjust their task strategy after reward contingencies were switched. Isolation-reared rats also completed fewer trials and exhibited lower levels of overall activity in the probabilistic reversal-learning task than did the socially reared rats. This finding contrasted with the elevated levels of unconditioned investigatory activity and reduced levels of locomotor habituation that isolation-reared rats displayed in the behavioral pattern monitor. Finally, isolation-reared rats also exhibited sensorimotor gating deficits, reflected by decreased prepulse inhibition of the startle response, consistent with previous studies. We concluded that isolation rearing constitutes a valuable, noninvasive manipulation for modeling schizophrenia-like cognitive deficits and assessing putative therapeutics.

Keywords Isolation rearing · Probabilistic learning · Reversal learning · Prepulse inhibition · Behavioral pattern monitor · Schizophrenia · Habituation · Investigatory behavior · Startle response · Rats

Isolation rearing is a neurodevelopmental manipulation developed to mimic psychosocial deprivation. Social isolation of rodents after weaning produces permanent neurochemical, structural, and behavioral alterations (Bianchi et al., 2006; Fone & Porkess, 2008; C. A. Jones, Brown, Auer, & Fone, 2011; King, Seeman, Marsden, & Fone, 2009; Powell, 2010; Schubert, Porkess, Dashdorj, Fone, & Auer, 2009). At least some of these effects, such as disruptions in sensorimotor gating, are developmentally specific, in that they result only when animals are isolated as juveniles; social isolation of rodents after they have reached adulthood does not produce these alterations (Cilia, Reavill, Hagan, & Jones, 2001; Wilkinson et al., 1994).

Early-life stressors have been associated with neuropsychiatric vulnerability and an increased risk of several mental illnesses, including schizophrenia (Agid et al., 1999;Lim, Chong, & Keefe, 2009). Moreover, social isolation and impaired social functioning are nonspecific symptoms of schizophrenia that have been observed to predate the onset of psychotic symptoms in both retrospective and prospective studies (Addington, Penn, Woods, Addington, & Perkins, 2008; Häfner, Löffler, Maurer, Hambrecht, & an der Heiden, 1999; Møller & Husby, 2000) and that can predict conversion to psychosis in high-risk patients (Cannon et al., 2008). Notably, several of the abnormalities produced by isolation rearing strongly resemble findings in human schizophrenia (Fone & Porkess, 2008; Geyer, Wilkinson, Humby, & Robbins, 1993; Powell, 2010). For example, prepulse inhibition (PPI) of the startle response, an operational measure of sensorimotor gating, is robustly decreased in patients with schizophrenia (Braff, Geyer, & Swerdlow, 2001;Braff, Grillon, & Geyer, 1992;Braffetal.,1978), possibly reflecting a pervasive information-processing deficit (Braff & Geyer, 1990). Isolation rearing reliably decreases PPI in rats (Cilia, Hatcher, Reavill, & Jones, 2005; Cilia et al. …

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