Prolonged perinatal exposure to AZT affects aggressive behaviour of adult CD-1 mice

Rationale: AZT is commonly administered to seropositive women and their neo nates to prevent mother-to-child transmission of HIV. Recently, animal stud ies performed in monkeys and rodents have revealed that pre- and/or perinat al exposure to AZT induces age- and sex-dependent behavioural alterations i n the offspring, possibly resulting from an action of this drug on CNS targ ets. Long-term effects of prenatal AZT treatment on social/aggressive behav iour of adult male mice have been previously described. Specifically, AZT h as been shown to induce selective changes in the offensive components of ag onistic interactions. Objective: The aim of the present study was to extend previous findings, analysing the long-term effects of a more prolonged AZT exposure on intraspecific male mice agonistic behaviour. Methods: AZT was given or ally twice daily to pregnant CD-I mice. The dosage selected for AZ T was 160 mg/kg. Saline solution (0.9% NaCl) was used as vehicle. Star ting on postnatal day (PND) 60 isolated males underwent five 15-min repeated en counters with an opponent of the same age and strain isolated for the same amount of time. Furthermore, a locomotor activity test (PND 67) and a hot-p late test (52+/-0.1 degrees C) (PND 74) were performed to assess AZT effect s on, respectively, general activity and pain sensitivity. Results: AZT per inatal exposure reduced attack behaviour of adult mice, while increasing th e likelihood of them behaving as subordinates. Furthermore, long-term effec ts of AZT treatment on pain sensitivity were found in the hot-plate test, w ith AZT mice showing higher pain thresholds than controls. Conclusions: Ove rall, these data indicate that perinatal exposure to drugs such as AZT exer ts selective effects on the developing CNS, resulting in long-term behaviou ral disturbances. Future studies will need to address the issue of the spec ific mechanisms underlying these effects.