Neurobehavioral effects of prenatal lamivudine (3TC) exposure in preweaning mice.
The present study provides a characterization of the behavioral changes induced in preweaning mice by prenatal exposure to lamivudine (3TC), an antiviral drug recently entered in the clinical practice to treat HIV patients. Pregnant CD1 mice were given per os bidaily either 3TC at different doses (125, 250, or 500 mg/kg) or vehicle solution (saline 0.9%) from pregnancy day 10 to delivery. Data on reproductive performance, such as gestation length, litter size, and offspring viability, were collected. Offspring were then examined for a series of different somatic and behavioral end points, including sensorimotor development, ontogenetic pattern of ultrasonic vocalization, passive avoidance learning, and locomotor activity. In the absence of gross changes in somatic and sensorimotor development, a slight change in ultrasound emission was found on postnatal day (PND) 3, with 125 and 500 mg/kg 3TC-treated offspring emitting a lower number of ultrasounds. Learning and retention performances of a passive-avoidance task on PND 20-21 were unaffected by 3TC treatment, while decreased habituation in an automated locomotor activity test was evident in male offspring exposed to 250 and 500 mg/kg 3TC.
Calamandrei
G
G
Comparative Psychology Section, Laboratorio di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanità, Rome, Italy. gemma@iss.it
Venerosi
A
A
Branchi
I
I
Valanzano
A
A
Puopolo
M
M
Alleva
E
E
D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects*; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects; D019259:Lamivudine / Q000009:adverse effects*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D051379:Mice; D011247:Pregnancy; D014886:Weaning
D019380:Anti-HIV Agents; D019259:Lamivudine