Increased Dopamine DHigh2 Receptors in Rats Reared in Social Isolation

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ABSTRACTPostweaning social isolation in the rat induces lasting alterations that parallel several of the core symptoms seen in human schizophrenics, including hyperreactivity to novel environments, cognitive impairment, and deficits in sensorimotor gating. The current study determined whether these changes are accompanied by any elevation in the proportion of striatal dopamine receptors in the functional high affinity state (DHigh2), as observed in other preclinical models of psychosis. Male Lister hooded rats (20-24 days) were housed in groups of three or alone. On Day 36 postweaning locomotor activity was monitored for 60 min in a novel arena, and on Day 37 novel object discrimination was assessed using a 2 h intertrial interval. Three days later striata were collected, homogenized, washed three times to remove endogenous dopamine, and the proportion of DHigh2 determined by competition between dopamine and 2.27 nM [3H]domperidone. Isolates were significantly more active than group housed controls for both ambulation and rears. Although both groups exhibited comparable levels of familiarization trial object exploration, group housed animals were able to discriminate between novel and familiar objects during the choice trial while isolates were not. Social isolation was associated with a highly significant elevation in the proportion of striatal DHigh2, equivalent to a 3.3-fold increase (group 15.2% ± 1.4%, isolate 49.8% ± 4.8%; P < 0.0001, Student's unpaired t-test). These findings support both the hypothesis that elevated DHigh2 is a common feature of multiple animal models of psychosis, and the validity of isolation rearing as a neurodevelopmental model of a “schizophrenia-like” state. Synapse 63:476-483, 2009. © 2009 Wiley-Liss, Inc.

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