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Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
Published on: February 18, 2016
Exposure to lidocaine in early life does not cause negative long-term behavioural changes in mice
Sonja Buratovic1, Gaetan Philippot1, Bo Stenerlöw2
1Toxicology and Drug Safety, Department of Pharmaceutical biosciences, Uppsala University, Uppsala, Sweden.
Insights
Neonatal exposure to the local anesthetic lidocaine did not cause long-term behavioral issues in mice. This study provides reassurance for using lidocaine to treat seizures in premature infants.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Lidocaine is a local anesthetic frequently used in neonatal intensive care units for treating seizures in premature infants.
- Concerns exist regarding potential long-term behavioral effects of early-life exposure to antiepileptic drugs, based on animal model studies.
- Limited data exists on the long-term behavioral outcomes of neonatal lidocaine exposure.
Purpose of the Study:
- To investigate the long-term behavioral effects of neonatal lidocaine exposure in a mouse model.
- To assess potential adverse behavioral outcomes following early-life exposure to lidocaine during a critical brain development period.
Main Methods:
- Neonatal mice were administered subcutaneous injections of saline (control) or varying doses of lidocaine (0.5, 4, or 12 mg/kg) on postnatal day 10.
- A sensitive behavioral test was employed at 2 and 6 months of age to detect long-term alterations.
- The behavioral test assessed habituation to a novel home environment.
Main Results:
- All animals survived the study period without acute toxicity.
- Lidocaine exposure did not lead to any observable negative behavioral effects at either 2 or 6 months of age.
- No significant differences in habituation to a new environment were noted between lidocaine-exposed and saline-treated groups.
Conclusions:
- Neonatal exposure to lidocaine does not appear to induce negative long-term behavioral effects in mice when administered during early life.
- These findings are reassuring for the clinical practice of using intravenous lidocaine to manage seizures in premature infants.
- Further research may explore other sensitive behavioral domains or different exposure paradigms.
Background:
The local anaesthetic lidocaine is widely used in the neonatal intensive unit to treat seizures in premature babies. However, other antiepileptics administered during early development in various animal models have shown negative long-term behavioural effects. Since no long-term behavioural data so far exist regarding lidocaine exposure at an early age, we decided to perform this extended follow-up study using a sensitive behavioural test.
Methods:
Neonatal mice received a subcutaneous administration of saline or one dose of lidocaine (0.5, 4, or 12 mg kg-1) on postnatal day 10 (P10; peak of the Brain Growth Spurt). A well-established test to detect long-term behavioural alterations was conducted at 2 and 6 months of age, corresponding to early and late adulthood in humans.
Results:
All animal survived to later testing. No signs of acute toxicity were observed. Lidocaine exposure did not result in any negative behavioural effects during habituation to a new home environment at any of the two studied time points, compared to saline placebo.
Conclusions:
Lidocaine does not by itself produce any negative long-term behavioural effects in mice exposed in early life (P10) despite long-term follow-up. This is reassuring regarding the current practice of treating seizures in premature babies with intravenous lidocaine.

