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Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats
Published on: December 14, 2014
Neonatal exposure to phenobarbital potentiates schizophrenia-like behavioral outcomes in the rat
S K Bhardwaj1, P A Forcelli, G Palchik
1Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Insights
Neonatal exposure to phenobarbital, an antiepileptic drug (AED), can lead to schizophrenia-like behaviors in adulthood. This highlights AEDs as potential risk factors for later-life neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Early-life seizures are linked to increased schizophrenia risk.
- Antiepileptic drugs (AEDs) like phenobarbital are used to treat early-life seizures.
- The impact of neonatal AED exposure on later psychiatric outcomes requires investigation.
Purpose of the Study:
- To test if neonatal phenobarbital exposure increases schizophrenia-like behaviors in adult rats.
- To evaluate phenobarbital's effects in a rat model of schizophrenia (neonatal ventral hippocampal lesion).
Main Methods:
- Neonatal rats received a single dose of phenobarbital.
- Behavioral tests included amphetamine-induced locomotion, prepulse inhibition, elevated plus-maze, and novel object recognition.
- Compared outcomes in phenobarbital-exposed rats, rats with neonatal lesions, and control rats.
Main Results:
- Neonatal phenobarbital exposure alone disrupted sensorimotor gating (prepulse inhibition).
- This disruption was comparable to that caused by neonatal lesions.
- Phenobarbital exposure enhanced adult locomotor response to amphetamine, with or without lesions.
Conclusions:
- Neonatal phenobarbital exposure can predispose rats to schizophrenia-like behavioral abnormalities.
- AED exposure in early life may be a risk factor for adult neuropsychiatric disorders.
- Further clinical research is needed to examine AEDs as risk factors in human populations.
Abstract:
Previous work has indicated an association between seizures early in life and increased risk of psychiatric disorders, including schizophrenia. However, because early-life seizures are commonly treated with antiepileptic drugs (AEDs) such as phenobarbital, the possibility that drug treatment may affect later-life psychiatric outcomes needs to be evaluated. We therefore tested the hypothesis that phenobarbital exposure in the neonatal rat increases the risk of schizophrenia-like behavioral abnormalities in adulthood. Thus, in this study, we examined the effects of a single acute neonatal exposure to phenobarbital on adult behavioral outcomes in the rat neonatal ventral hippocampal (nVH) lesion model of schizophrenia. We compared these outcomes to those in rats a) without nVH lesions and b) with nVH lesions, without phenobarbital. The tasks used for behavioral evaluation were: amphetamine-induced locomotion, prepulse inhibition, elevated plus-maze, and novel object recognition task. We found that neonatal phenobarbital treatment (in the absence of nVH lesions) was sufficient to disrupt sensorimotor gating (as tested by prepulse inhibition) in adulthood to an extent equivalent to nVH lesions. Additionally, neonatal phenobarbital exposure enhanced the locomotor response to amphetamine in adult animals with and without nVH lesions. Our findings suggest that neonatal exposure to phenobarbital can predispose to schizophrenia-like behavioral abnormalities. Our findings underscore the importance of examining AED exposure early in life as a potential risk factor for later-life neuropsychiatric abnormalities in clinical populations.
