HISTOLOGICAL EFFECTS AND NEUROBEHAVIOURAL PATTERNS OF TRAMADOL ON THE PREFRONTAL CORTEX AND HIPPOCAMPUS IN THE ADULT WISTAR RAT

ABSTRACT

Tramadol hydrochloride (TH) is a centrally acting analgesic with opioid activities used for treating moderate to severe pain with fewer side effects than traditional opioid medications. The present work aimed to study the dose-dependent possible deleterious effect of long-term administration of Tramadol on the structural architecture of the Prefrontal cortex and hippocampus. It was also aimed at determining whether Tramadol hydrochloride can increase oxidative stress, access the neurobehavioural pattern in high doses of Tramadol, as well as a fourteen days (14) spontaneous recovery period to evaluate the reversibility of the toxic effects on the brain tissues of the rats. Fifty (50) adult Wistar rats were divided into nine (9) groups. Group A: Each animal received distilled water for sixty (60) days and were used as control. Group B1: Each animal received 400mg/kg/day of Tramadol orally for sixty (60) days. Group B2: Each animal received the same dose as group B1, then kept fourteen (14) days later in order to study the effect of withdrawal. Group C1: Each animal received 800mg/kg/day of Tramadol orally for sixty (60) days. Group C2: Each animal received the same dose as group C1, then kept fourteen (14) days later in order to study the effect of withdrawal. Group D1: Each animal received 1600mg/kg/day of Tramadol orally for sixty (60) days. Group D2: Each animal received the same dose as group D1, then kept fourteen (14) days later in order to study the effect of withdrawal. Group E1: Each animal received 3200mg/kg/day of Tramadol orally for sixty (60) days. Group E2: Each animal received the same dose as group E1, then kept fourteen (14) days later in order to study the effect of withdrawal. Neurobehavioural tests were carried out before and after the administration. At the end of experimental period, rats were sacrificed by cervical dislocation and decapitated. The brain were extracted from the skull and fixed in 10% formal calcium and phosphate buffer for histopathological and biochemical test respectively .It was then stained in H&E and Cresyl Fast Violet (CFV). The results showed that high doses of TH produced remarkable histomorphological changes inprefrontal cortex (PFC) and hippocampus (HC) as compared to control. The withdrawal groups showed a severe deterioration than the non-withdrawal groups.Tramadol not only induced oxidative stress in brain, but also was associated with significant decrease in brain Glutathione peroxidase. It also yielded increased malondialdehyde (MDA) level, which suggested increased lipid peroxidation. Tramadol decreased anxiety (anxiolytic) and does not affect memory as evident by the neurobehavioural tests. The study concluded that Tramadol damaged the cytoarchitecture of the hippocampus and Prefrontal cortex, it is an anxiolytic agent and does not affect memory except in the highest dose.