Prenatal exposure to anti-HIV drugs - Long-term neurobehavioral effects oflamivudine (3TC) in CD-1 mice

The present study was aimed at investigating the long-term effects of prena tal exposure to lamivudine (3TC), an antiretroviral drug used in clinical p ractice alone or in combination with zidovudine (AZT) to prevent mother-to- child transmission of the HIV virus. Pregnant CD-I mice were given per os t wice daily either 3TC at different doses (125, 250, or 500 mg/kg) or vehicl e solution (NaCl 0.9%) from pregnancy day 10 to delivery, Offspring behavio r was examined on postnatal day 35 in a 20-min social interaction test. At adulthood different behavioral endpoints were analyzed, including locomotor activity and exploration in an open field following administration of the muscarinic antagonist scopolamine (2 mg/kg), spatial learning in either rad ial arm or Morris water maze, virgin female behavior in a maternal inductio n test, and pain sensitivity in a hot-plate test (52 +/- 0,1 degrees C). Ou r findings confirm the low neurotoxicity of 3TC in comparison to AZT. Howev er some significant behavioral alterations were found, namely (I) a decreas e in immobility in the open field test, (2) an increase in the responsivene ss to scopolamine shown by the 500-mg/kg 3TC mice (sniffing behavior) in th e open field, and (3) a longer escape latency in the first day of the rever sal phase in the Morris task (particularly marked in the 250-mg/kg treatmen t group). No significant changes in either pain sensitivity, social/affilia tive, or maternal behavior were found, although a higher occurrence of aggr essive behavior toward foster pups was noted in both 125- and 500-mg/kg 3TC females. (C) 2000 Elsevier Science Inc. All rights reserved.