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

Int J Neurosci. 2020 Sep;130(9):898-905. doi: 10.1080/00207454.2019.1709841. Epub 2020 Jan 6.

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.

MeSH terms

  • Animals
  • Animals, Newborn
  • Anxiety* / chemically induced
  • Anxiety* / physiopathology
  • Behavior, Animal* / drug effects
  • Behavior, Animal* / physiology
  • Buprenorphine / administration & dosage
  • Buprenorphine / pharmacology*
  • Female
  • Locomotion / drug effects
  • Locomotion / physiology
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Methadone / administration & dosage
  • Methadone / pharmacology*
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Narcotics / administration & dosage
  • Narcotics / pharmacology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / chemically induced
  • Prenatal Exposure Delayed Effects* / physiopathology
  • Rats
  • Rats, Wistar
  • Seizures* / chemically induced
  • Seizures* / physiopathology
  • Sex Factors
  • Tramadol / administration & dosage
  • Tramadol / pharmacology*

Substances

  • Narcotics
  • Tramadol
  • Buprenorphine
  • Morphine
  • Methadone