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Updated: May 18, 2026
Behavioral Characterization of Pentylenetetrazole-induced Seizures: Moving Beyond the Racine Scale
Published on: July 8, 2025
Morphine exposure induces age-dependent alterations in pentylenetetrazole-induced epileptic behaviors in prepubertal
Morteza Gholami1, Ehsan Saboory
1Faculty of Science, Department of Biology, University of Urmia, Urmia, Iran.
Insights
Neonatal morphine exposure increases seizure susceptibility in young rats, but this effect is reversed in older prepubertal rats. This age-dependent impact on pentylenetetrazole-induced seizures highlights critical developmental windows.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Opioids can influence epilepsy development, exhibiting both pro- and anti-epileptogenic properties.
- Understanding the long-term neurological effects of early opioid exposure is crucial for assessing developmental risks.
Purpose of the Study:
- To investigate the hypothesis that neonatal morphine administration alters seizure susceptibility in prepubertal rats.
- To determine if these effects are age-dependent in later developmental stages.
Main Methods:
- Neonatal female rats received subcutaneous injections of morphine or saline on postnatal days 8-14.
- Animals were re-treated with morphine or saline on postnatal day 25 or 32.
- Seizure susceptibility was assessed using the pentylenetetrazole (PTZ)-induced seizure model.
- Blood corticosterone levels were measured.
Main Results:
- Morphine administration at P25 decreased seizure latency and increased seizure rates.
- These effects were reversed at P32, with morphine increasing latency and decreasing seizure rates.
- Blood corticosterone levels were significantly higher in P32 rats compared to P25 rats.
- Significant age-dependent differences in seizure behavior were observed between P25 and P32 rats.
Conclusions:
- Neonatal morphine exposure increases seizure vulnerability in P25 prepubertal rats.
- This vulnerability is not present in P32 rats, indicating an age-dependent effect.
- Early chronic morphine exposure in infant rats can modify susceptibility to PTZ-induced seizures in an age-dependent manner.
Abstract:
Opioids show both pro- and anti-epileptogenic effects in different experimental models of epilepsy. In the present study, the pentylentetrazole (PTZ)-induced seizure model was used to test the hypothesis that neonatal morphine administration affects seizure susceptibility in prepubertal rats. Female rats were subcutaneously injected with either morphine or saline on postnatal days 8-14 (P8-P14). To verify the long-term effect of morphine (or saline), the animals were treated second time with morphine (21 mg/kg; or saline) on either P25 or P32. Morphine administration decreased latency of myoclonic jerks and time to onset and increased tonic-clonic seizure rate at P25, but these findings were inversed at P32. Results showed a significant age difference in seizure behaviors between P25 and P32 animals. Blood corticosterone (COS) levels were significantly higher in P32 rats than in P25 rats. These findings show that neonatal morphine exposure plays an important role in increasing seizure vulnerability in P25 prepubertal rats but not in P32 rats. We conclude that early exposure to chronic morphine in infant rats might change their susceptibility to PTZ-induced seizure in an age-dependent manner.
