Behavioral effects of prenatal exposure to lidocaine in the rat: effects of dosage and of gestational age at administration.

Pregnant Long-Evans hooded rats were dosed via injections into the gum with 3, 6, or 9 mg/kg lidocaine, or vehicle, or were uninjected, on gestational day 4 (GD4), GD11, or GD18. Offspring (8-11 litters/group) were tested on a variety of tests of behavioral development and adult behavior. No effects of any dose at any time of administration were found upon maternal weight gain in gestation, litter size, or initial birth weight or weight gain of the pups. Administration at GD4 produced few effects; only footshock sensitivity showed a significant effect of dosing, although there were trends toward dosing effects on spontaneous alternation. For administration on GD11, lidocaine was associated with slight but significant alterations in sex ratios, and a trend toward drug effects on development of spontaneous alternation. Vehicle administration at this age reduced barbiturate sleep time in offspring and slightly altered footshock sensitivity. Lidocaine dosing on GD18 was associated with a number of significant alterations of behavior, including visual discrimination, shuttlebox avoidance, tail flick, and water maze errors; there were also both vehicle and lidocaine effects on water maze latencies. These data reinforce our previous report that lidocaine may be a behavioral teratogen, and suggest that administration in later gestation in the rat may alter a broader range of behaviors than earlier in gestation.