Behavioral effects of mid-pregnancy administration of lidocaine and mepivacaine in the rat.
Sperm-positive female Long-Evans hooded rats were injected with 6 mg/kg lidocaine (with epinephrine), 6 mg/kg mepivacaine, or saline, into the masseter muscle of the jaw on Day 11 of gestation. Birth, growth, and litter composition were unaffected by the drug treatment, as was shuttle box acquisition. Offspring of drug-treated dams had longer latencies than controls on the first day of negative geotaxis training, and were more sensitive to electric footshock. Lidocaine-dosed offspring responded less in the presence of the correct cue in the visual discrimination task, and mepivacaine-dosed animals were hypoactive in the open field. In a second study, offspring of lidocaine-dosed dams were slower to develop the righting reflex, made more errors in acquiring a water maze, had longer suppression times in a conditioned suppression task, and had longer latencies in the tail flick test. Dosing had no effect upon birth and growth, shuttle box, or footshock sensitivity. These data demonstrate that midgestational exposure to lidocaine or mepivacaine at a dose near the limits of permissible human exposure produces significant behavioral changes in the offspring. This preliminary study suggests that development of some portion of the central nervous system is altered by such exposure. Further work is required to determine the parameters and the extent of the effect.
R F
RF
Smith
G G
GG
Wharton
S L
SL
Kurtz
K M
KM
Mattran
A R
AR
Hollenbeck
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D005260:Female; D008012:Lidocaine / Q000633:toxicity*; D008431:Maternal-Fetal Exchange; D008619:Mepivacaine / Q000633:toxicity*; D009420:Nervous System / Q000254:growth & development; D009422:Nervous System Diseases / Q000139:chemically induced*; D010146:Pain / Q000503:physiopathology; D010468:Perceptual Disorders / Q000139:chemically induced; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D014796:Visual Perception
D008012:Lidocaine; D008619:Mepivacaine