Acute and Chronic Tramadol-Induced Cognitive Changes in Male Sprague-Dawley Rats
Résumé
Cognitive impairment is a risk factor for falls, particularly true in the elderly due to age-related decline. Chronic drug consumption, often encountered in the elderly, has been reported to increase this risk, although underlying mechanisms remain to be uncovered (cumulative effect due to chronic use or increased half-life/higher sensitivity). Among opioid drugs mostly prescribed in elderly within European countries, tramadol is associated with a risk of falls. Herein, we investigated the different types of cognitive processes affected after acute or chronic tramadol administration. We conducted a 6-week longitudinal study in 24 adult rats, divided into 3 groups receiving daily administration (OG) of either saline or tramadol at 25 or 50 mg/kg. The locomotor effect of a single administration was assessed over a 24-hour period. Residual cognitive effects were then assessed using the MWM (after 1, 2, and 6 weeks of administration) to evaluate spatial recognition memory, and the ORT (after week 4 of administration and 6 weeks after the last administration) to assess episodic-like memory. A low dose of tramadol decreased locomotor activity, whereas a high dose increased it. In the MWM test, a high dose of tramadol impaired retention performance, and both doses impaired ORT performance. This latter ORT deficit persisted after a 6-week washout period. This study suggests that tramadol administration induces two types of cognitive dysfunction. Since tramadol has significant anticholinergic activity, hyperactivity observed after a single high dose could be considered delirium-like behavior. Altered spatial recognition memory after chronic administration, without impairing learning performance, could be explained by hippocampal involvement.
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