Diazepam and caffeine administration during the first week of life: Changes in neonatal and adolescent behavior

Abstract

The male offspring of hooded Lister rats were fostered at birth into 23 experimental litters. One pup in each litter was allocated to each of the following treatment groups: vehicle control; caffeine (15 or 30 mg/kg); diazepam (10 mg/kg, alone or plus caffeine 15 or 30 mg/kg). Pups were given daily injections on neonatal days 1–7 and were observed for 15 min following each injection. Diazepam significantly increased paddling and forward walking, particularly on days 5 and 7; caffeine also increased these behaviors, but less markedly. Diazepam increased the incidence of clonic jerks, particularly on day 7 and increased the spontaneous loss of righting reflex. The pups were then left undisturbed until weaning at day 21 and testing from days 35–42. There were no lasting effects of the neonatal treatments in two tests of anxiety, or in passive avoidance performance. Rats that had been treated neonatally with diazepam had significantly lower motor activity scores and reared less in the holeboard than did controls, and neonatal treatment with caffeine also resulted in lower motor activity scores. Neonatal treatment with caffeine made rats more aggressive (increased kicking and pushing) when they were intruding into another rat's territory. Neonatal treatment with diazepam increased aggression in resident rats, and this was counteracted by neonatal treatment with caffeine. Neonatal caffeine treatment enhanced rats' unconditioned preference for the black chamber in a black-white preference test and neonatal diazepam treatment reduced it.