Effects of neonatal administration of diazepam and lorazepam on performance of adolescent rats in tests of anxiety, aggression, learning and convulsions.

Abstract

Male offspring of hooded Lister rats were fostered at birth and allocated to experimental litters of eight, in which at least one rat was allocated to every treatment group. Vehicle control, diazepam (1 or 10 mg/kg) or lorazepam (0.25 or 2.5 mg/kg) were administered daily from postnatal day 1-21. Rats were tested undrugged at adolescence (days 35-41). Neonatal treatment with diazepam (10 mg/kg) or lorazepam (2.5 mg/kg) tended to increase active social interaction, perhaps indicative of an anxiolytic effect. These treatments also increased unpunished licking, but were without effect on punished drinking. When the experimental rats were resident in their home-cages the effect of neonatal treatment with diazepam (1 mg/kg) was to increase the number of offensive behaviors directed at an untreated intruder. In contrast, neonatal treatment with lorazepam (2.5 mg/kg) increased the frequency and duration of submissions to the intruder. When the rats that had been treated neonatally were intruding into the territory of an untreated resident rat, diazepam treatment (10 mg/kg) increased wrestling, whereas lorazepam (0.25 mg/kg) decreased sniffing and kicking the resident. The neonatal treatments did not affect acquisition or short-term retention of a passive avoidance response, but the re-entry latencies indicated poorer long-term retention by diazepam-treated rats. The neonatal treatments did not change the threshold for convulsions to pentylenetetrazole.