Social behavior represents an integral part of behavioral repertoire of rats particularly sensitive to pharmacological and environmental influences. The aim of the present study was to investigate whether early postnatal clonazepam (CZP) exposure can induce age-dependent changes related to expression of social behavior. The drug was administered from postnatal day (P) 7 until P11 at daily doses of 0.1, 0.5 and 1.0 mg/kg i.p. We designed three experiments to assess whether exposure to CZP affects social behavior in respect to the age of rats and the test circumstances, specifically their familiarity with test conditions during adolescence (P32), social behavior in juveniles and adolescents (P18-P42) and social behavior in a resident-intruder paradigm. The frequency and duration of a various patterns of social behavior related to play and social investigation not related to play were evaluated. The results showed that CZP postnatal exposure decreased social play behavior regardless of age and familiarity or unfamiliarity of experimental environment but did not affect the social investigation per se. When rats were confronted with an intruder in their home cages intense wrestling and inhibition of genital investigation were found. In conclusion, these findings show that short-term CZP postnatal exposure inhibits social play behavior and alters specific patterns of social behavior in an age and environment related manner.
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Clinical and experimental studies suggest possible risks associated with the repeated administration of benzodiazepines (BZDs) during the prenatal or early postnatal period on further development and behavior. In the present study, we assess short- and long-term effects of early exposure to clonazepam (CZP) on cognitive tasks. CZP (0.5 or 1.0 mg/kg/day) was administered from postnatal day (P)7 until P11, and animals were exposed to the following behavioral tests at different developmental stages: (1) a homing response (HR) test, which exploits the motivation of a rat pup to reach its home nest, was administered on P12, P15, P18 and P23 rats; (2) passive avoidance was tested in three trials (at 0, 2 and 24 h intervals) on P12, P15, P18, P25 and P32 rats; (3) within- and between-session habituation was tested in an open field (OF) at P70; and (4) a long-term memory (LTM) version of the Morris water maze (MWM) was tested at P80. A 1.0 mg/kg dose of CZP extended latency in the HR and decreased the number of correct responses when tested at P12 and P23. In the first trial of the passive avoidance test, latency to enter a dark compartment was shorter in the CZP-exposed rats. Both treated and control animals older than P15 learned the passive-avoidance response at the same rate. Irrespective of the treatments, all adult animals showed within-session habituation. Between-session habituation, however, was found only in the controls. With respect to the MWM test, all animals learned to reach the platform, but animals exposed to higher doses of CZP spent more time swimming in the first acquisition test. No difference between groups was found in a repeated acquisition test (10 and 40 days after the first acquisition test). The results of the present study show that even short-term exposure to CZP alters behavioral responsiveness in pre-weaning, juvenile and adult animals. Not only were changes observed on conventional cognitive tests in our study, but the changes also seem to be related to emotional/motivational responsiveness.
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