Morphine exposure induces age-dependent alterations in pentylenetetrazole-induced epileptic behaviors in prepubertal rats.

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.