Mefenamic Acid Attenuates Intracerebroventricular Streptozotocin-Induced Cognitive Deficits in the Rat: A Behavioral Analysis

Intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats is followed by long-term and progressive deficits in learning, memory, and cognitive performance which is somewhat similar to sporadic Alzheimer’s disease (SAD). Epidemiological studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs) could delay or slow the clinical expression of SAD. Therefore, the beneficial effect of mefenamic acid (MA) was investigated on ICV STZ-induced learning, memory, and cognitive impairment in male rats. For this purpose, rats were injected with ICV STZ bilaterally, on days 1 and 3 (3 mg/kg). The STZ-injected rats received MA (30 mg/kg/day, i.p.) starting from day 5 post-surgery for two weeks. The learning and memory performance was assessed using passive avoidance paradigm, and for spatial cognition evaluation, radial eight-arm maze (RAM) task was used. It was found out that MA-treated STZ-injected rats show higher correct choices and lower errors in RAM than vehicle-treated STZ-injected rats. In addition, MA administration significantly attenuated learning and memory impairment in STZ-injected group in passive avoidance test. These results demonstrate MA efficacy against cognitive deficits as well as learning and memory impairment caused by ICV injection of STZ in rats and its potential in the treatment of some neurodegenerative disorders including SAD.