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Tramadol, a frequently used pain reliever drug, present neurotoxic effects associated to cognitive dysfunction. Moreover, crocin has been reported to have neuroprotective effects. The aim of this study was to assess crocin’s capacity to protect learning, and memory abilities on tramadol-treated rats. A total of 35 rats were divided into five groups: Control, Saline, tramadol (50 mg/kg), tramadol + crocin(30 mg/kg), crocin groups and treated orally for 28 consecutive days. Morris water maze (MWM) and passive avoidance (PA) tests were done, followed by dissection of the rat’s brains for toluidine blue and TUNEL staining. In MWM test, tramadol group spent lower time and traveled shorter distance in the target quadrant (Q1) (P < 0.05). On the other side, the traveled distance in tramadol-crocin group was higher than tramadol (P < 0.05). In PA test, both the delay for entering the dark, and the total time spent in the light compartment decreased in tramadol comparing to the control group (P < 0.05), while it increased in tramadol-crocin compared with the tramadol group (P < 0.05). In tramadol-treated animals, the dark neurons (DNs) and apoptotic cells in CA1, CA3 and DG increased (P < 0.05), while concurrent intake of crocin decreased the number of DNs and apoptotic cells in these areas (P < 0.05). Crocin was able to improve learning and memory of tramadol-treated rats and also decreased DNs and apoptotic cells in the hippocampus. Considering these results, the potential capacity of crocin for decreasing side effects of tramadol on the nervous system is suggested.

Nanoscale titanium dioxide (TiO2), which is massively produced and widely used in living environment, seems to have a potential risk on human health. The central nervous system (CNS) is the potential susceptible target of nanoparticles, but the studies on this aspect are limited so far. The aim of this study was to evaluate the effects of exposure to TiO2 nanoparticles during lactation period on learning and memory of offspring. Lactating Wistar rats were exposed to TiO2 nanoparticles (100 mg/kg; gavage) for 21 days. The Morris water maze and passive avoidance tests showed that the exposure to TiO2 nanoparticles could significantly impair the memory and learning in the offspring. Therefore, the application of TiO2 nanoparticles and the effects of their exposure, especially during developmental period on human brain should be cautious.

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