Date of Defense


Date of Graduation




First Advisor

Lisa Baker

Second Advisor

Rachel Burroughs

Third Advisor

Jake Spitsbergen


Tramadol, Radial arm maze, Spatial memory, Behavior, Rats


Tramadol hydrochloride is a synthetic analogue of codeine frequently used for pain management with an analgesic potency comparable to pethidine. Tramadol is a mu opioid agonist reported to pose a decreased risk of abuse and a lower incidence of adverse side effects in comparison to other opioid analgesics. However, some reports indicate tramadol may produce cognitive impairment. Despite evidence of widespread use and abuse of tramadol, a review of recent literature has revealed few published studies on the drug’s adverse cognitive side effects. The present study assessed the radial eight-arm maze (RAM) performance of male Sprague-Dawley rats following a single acute dose and repeated daily injections of tramadol. Following three days of radial arm maze habituation, rats completed daily training in the RAM for 30 days to establish a performance baseline. On day 31, rats were given a single injection of tramadol (20 mg/kg) or an equivalent volume of 0.9% saline 30 min prior to assessment of maze performance. Once daily injections of tramadol or saline continued for an additional 20 days, while RAM training was suspended. On day 21, RAM performance was re-assessed to determine the effects of chronic treatment. Training continued for an additional 10 days to assess relearning. Both acute and chronic tramadol treatment increased the latency to complete the maze trial. However, working memory and reference memory, and percent correct trials did not differ significantly between treatment and control groups. Moreover, re-acquisition did not differ between the two groups over the 10 days following the end of treatment. These findings indicate tramadol poses low risk for cognitive impairment. Future investigations with a wider dose range, longer treatment duration, and other behavioral assessments are warranted to fully characterize tramadol’s neurocognitive effects.

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Honors Thesis-Restricted

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