Prenatal exposure to anti-HIV drugs. long-term neurobehavioral effects of lamivudine (3TC) in CD-1 mice.
The present study was aimed at investigating the long-term effects of prenatal exposure to lamivudine (3TC), an antiretroviral drug used in clinical practice alone or in combination with zidovudine (AZT) to prevent mother-to-child transmission of the HIV virus. Pregnant CD-1 mice were given per os twice daily either 3TC at different doses (125, 250, or 500 mg/kg) or vehicle solution (NaCl 0. 9%) from pregnancy day 10 to delivery. Offspring behavior 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 radial arm or Morris water maze, virgin female behavior in a maternal induction test, and pain sensitivity in a hot-plate test (52 +/- 0.1 degrees C). Our findings confirm the low neurotoxicity of 3TC in comparison to AZT. However some significant behavioral alterations were found, namely (1) a decrease in immobility in the open field test, (2) an increase in the responsiveness to scopolamine shown by the 500-mg/kg 3TC mice (sniffing behavior) in the open field, and (3) a longer escape latency in the first day of the reversal phase in the Morris task (particularly marked in the 250-mg/kg treatment group). No significant changes in either pain sensitivity, social/affiliative, or maternal behavior were found, although a higher occurrence of aggressive behavior toward foster pups was noted in both 125- and 500-mg/kg 3TC females.
Calamandrei
G
G
Section of Comparative Psychology, Laboratorio di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161, Rome, Italy. gemma@iss.it
Venerosi
A
A
Branchi
I
I
Valanzano
A
A
Alleva
E
E
D000818:Animals; D000831:Animals, Newborn; D019380:Anti-HIV Agents / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D007398:Interpersonal Relations; D019259:Lamivudine / Q000633:toxicity*; D008297:Male; D008425:Maternal Behavior / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011930:Reaction Time / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology
D019380:Anti-HIV Agents; D018727:Muscarinic Antagonists; D019259:Lamivudine; D012601:Scopolamine