Behaviorally timid rats respond differentially to conventional and atypical neuroleptics

An inhibited temperament can be manifested as simple shyness or as social phobia and is perhaps related to the extreme social dysfunction often accompanying schizophrenia. Here, we present a methodology for selecting subjects and testing changes in social attraction in an animal model of behavioral timidity. In Experiment 1, randomly selected female rats were chronically administered either vehicle only, the conventional neuroleptic haloperidol (0.1 mg/kg) or atypical drugs sulpiride (65 mg/kg) or clozapine (18 mg/kg). The animals were tested over 3 weeks for changes in attraction to a social stimulus. Findings revealed a statistically significant decrease in social investigation in the haloperidol treated animals compared to controls but no significant differences among the other groups. Experiment 2 employed pretests to select behaviorally timid (BT) animals. Only female rats having little initial attraction to unfamiliar non-social and social stimuli were chosen to serve as subjects for the experiment using the same drug exposure regiments and behavioral measures used in experiment 1. Results with pre-selected BT animals indicated that clozapine treated animals significantly increased social investigation whereas chronic exposure to either sulpiride or haloperidol groups did not increase social investigation. Indeed, haloperidol appears to have magnified avoidance of social contact. That there were minimal differences between drug groups on a measure of non-social general activity points to the beneficial increases in investigation from clozapine being specific to social inhibition. Conclusions are that timidity may involve aspects of the serotonergic system uniquely influenced by clozapine, and the animal model of the second experiment may prove useful for studies of the biological underpinnings of behavioral timidity. (c) 2005 Elsevier Inc. All rights reserved.