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Background and Aims: 3, 4- methylenedioxymethamphetamine (MDMA) is used for recreational purposes worldwide. The use of MDMA resulted in learning and memory dysfunction. Duloxetine, a serotonin/noradrenalin-reuptake inhibitor is also utilized to treat depression and anxiety. The current study aimed to evaluate the effects of duloxetine against MDMA's effect on anxiety, cognition, and memory disturbance in the male rats.
Materials and Methods: Wistar rats received treatment of saline (10 ml/kg; sham group), “MDMA” (10 mg/kg), “Duloxetine” (10 mg/kg), and Duloxetine plus MDMA (10 mg/kg, each), or no treatment (control) through the intraperitoneal administration for four days. The elevated plus maze (EPM), passive avoidance learning (PAL), Morris water maze (MWM), and novel object recognition (NOR) tests were employed to evaluate the anxiety, memory, and cognition,  
Results: The MDMA increased the time spent in open arms in EPM, time spent in the dark part of PAL, and swimming time to reach the platform in MWM. Furthermore, duloxetine inhibited the reduction of the discrimination index, time spent in the dark compartment, and time spent on the platform in NOR, PAL, and MWM tests among rats received MDMA. Moreover, duloxetine decreased time spent in open arms and the target quadrant in EPM and MWM tests.
Conclusions: Our findings suggested that duloxetine treatment attenuated the MDMA-induced anxiolytic response and could improve MDMA-induced cognitive impairment and disturbance in learning and memory.

Keywords: Anxiety, 3, 4- Methylenedioxymethamphetamine (MDMA), Learning and memory, Rat

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