G. Calamandrei et al., Effects of prenatal AZT+3TC treatment on open field behavior and responsiveness to scopolamine in adult mice, PHARM BIO B, 67(3), 2000, pp. 511-517
Treatment of pregnant seropositive women and their neonates with the nucleo
side analogs (reverse transcriptase inhibitors) zidovudine (AZT), lamivudin
e (3TC) and their combination has become a standard of care in industrializ
ed countries to prevent transmission of the HIV-1 virus. Animal studies ind
icated limited but significant behavioral changes in AZT or 3TC-prenatally
exposed offspring, whereas data on the potential neurobehavioral outcomes o
f AZT + 3TC combination are still lacking. The aim of the present study was
to assess in mice prenatally exposed to AZT + 3TC the functional state of
cholinergic muscarinic neuroregulation at adulthood. Pregnant CD-1 mice rec
eived per orem twice daily AZT + 3TC (160 and 500 mg/kg, respectively) or v
ehicle solution (NaCl 0.9%) from gestational day (GD) 10 to delivery (GD 19
). Locomotor activity, exploratory behavior and responsiveness to the musca
rinic cholinergic blocker scopolamine (2 mg/kg) were analyzed at adulthood
(PND 70) in offspring of both sexes in an open field lest. Results indicate
d that prenatal AZT + 3TC exposure does not influence responsiveness to the
muscarinic cholinergic antagonist as measured by analysis of the drug's ef
fects on locomotor and exploratory activity and different behavioral items.
However, AZT + 3TC-treated mice displayed higher frequency of oaring, and
lower frequency and duration of self-grooming behavior, consistent with an
effect on dopaminergic neurotransmission. However, this would need confirma
tory experiments. (C) 2000 Elsevier Science Inc. All rights reserved.