perinatal exposure to azt affects juvenile social

31° Congresso Nazionale della Società Italiana di Farmacologia
Trieste, 26-29 giugno 2003
PERINATAL EXPOSURE TO AZT AFFECTS JUVENILE SOCIAL INTERACTIONS
AND ADULT SOCIAL/AGGRESSIVE BEHAVIOUR OF CD-1 MICE
VENEROSI A*, CIRULLI F, ALLEVA E
Sections of *Comparative Psychology and Behavioural Pathophysiology, Laboratorio di
Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanità, Viale Regina Elena, 299, I00161 Rome, Italy, [email protected]
Zidovudine (AZT) is an effective treatment in preventing perinatal transmission of HIV-1. A
continuos re-evaluation of the risk- benefit ratio of human exposure to this drug is suggested
by both clinical and animal studies.. We report two studies aimed to verify the effects of a
prolonged AZT treatment – gestational period throughout delivery and during lactation – on
juvenile social interactions and on the intraspecific social/aggressive behaviour at adulthood in
CD-1 mice. Social behaviour represents a powerful and sensitive tool for an accurate
qualitative and quantitative assessment of subtle changes in brain function The dosage selected
for AZT was 160 mg/kg. Juvenile social behaviour of both male and female AZT exposed
mice was analysed on postnatal day (PND) 35 in a 30-min social interaction test.
Social/aggressive encounters were performed on PND60, and consisted of five 15-min
repeated fights with an opponent of the same age and strain isolated for the same amount of
time. Results show that on PND35, AZT exposure affected social behaviour of juveniles,
reducing aggressive grooming in males (p =.02), while decreasing investigative behaviour in
females diminishing the time spent sniffing and following the social partner (p = .04). At
adulthood, prolonged AZT exposure reduced attack behaviour of male mice (latency to the
first Attack p = .03; frequency and duration of Attack p = .08, p = .05 respectively), while
increasing the likelihood of them behaving as subordinates (frequency and duration of
submissive upright posture p = .03, p = .03 respectively; frequency of freezing p = .04). In
conclusion, these data indicate that prolonged exposure to AZT produces gender-dependent
behavioural disturbances of juvenile and adult mice when presented with a novel social
stimulus. Overall, these results, could advice clinicians to a long-term monitoring of exposed
children, in order to develop behavioural or biomedical interventions to counteract the adverse
consequences of developmental exposure to anti-HIV agents.
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