Long-time effects of prenatal morphine, tramadol, methadone, and buprenorphine exposure on seizure and anxiety in immature rats

Abstract

Purpose: This study aimed to investigate seizures and anxiety-like behaviors in immature rats prenatally exposed to opiate drugs.

Materials and methods: Pregnant rats were randomly divided into five groups: saline, morphine, tramadol, methadone, and buprenorphine. Administrations were performed intraperitoneally once a day for the last seven days of pregnancy. Neonatal rats were subdivided into ten groups, split according to sex. Anxiety-like behavior was tested on postnatal day (PD) 19. On PD 20, seizure was induced by PTZ injection.

Results: Morphine in male rats had an increased time to onset (p < 0.005), whereas there was a decreased number of tonic-clonic seizures in females (p < 0.05). Tramadol had an increased duration of tonic-clonic seizures compared to morphine and methadone in males (p < 0.005). Moreover, tramadol decreased open arm time and locomotor activity in males more than in females (p < 0.05). Methadone decreased open arm time in males (p < 0.05). Furthermore, buprenorphine and tramadol decreased open arm entrance in male rats (p < 0.05).

Conclusions: It was demonstrated that prenatal tramadol significantly increases both the duration of seizures and anxiety-like behaviors in immature male rats, whereas morphine decreases both of them. The effects of tramadol on seizure and anxiety-like behavior may be due to the comorbid occurrence of the symptoms of these two disorders.

Keywords:

• Anxiety
• buprenorphine
• methadone
• morphine
• prenatal
• seizures
• tramadol

Disclosure statement

The authors have no conflicts of interest.

Additional information

Funding

This study was supported by North Research Center, Pasteur Institute of Iran, Amol.