Journal of Behavioral and Brain Science, 2013, 3, 315-319 doi:10.4236/jbbs.2013.33031 Published Online July 2013 (http://www.scirp.org/journal/jbbs) Aqueous Extract of Saffron (Crocus sativus) Increases Brain Dopamine and Glutamate Concentrations in Rats Hosseinali Ettehadi 1 , Seyedeh Nargesolsadat Mojabi 2 , Mina Ranjbaran 2 , Jamal Shams 3 , Hedayat Sahraei 2* , Mahdi Hedayati 4 , Farzad Asefi 5 1 Institute of Science and Technology, Tehran, Iran 2 Neuroscience Research Center, Baqyiatallah (a.s.) University of Medical Sciences, Tehran, Iran 3 Department of Psychiatry, Faculty of Medicine, and Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4 Fat Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 5 Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Email: * h.sahraei@bmsu.ac.ir Received December 10, 2012; revised March 2, 2013; accepted March 20, 2013 Copyright © 2013 Hosseinali Ettehadi et al. This is an open access article distributed under the Creative Commons Attribution Li- cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Recent studies involving human and animal models have identified that saffron helps in the improvement of depression. Antidepressants are known to function in part by increasing brain serotonin, norepinephrine and dopamine concentra- tions. Therefore, to identify the cellular and molecular mechanism(s) underlying this property of saffron, we measured changes in rat brain dopamine, serotonin, norepinephrine and glutamate concentrations after administration of varying doses of an aqueous extract of saffron stigma. Male Wistar rats (250 ± 30 g) were administered a single dose of saffron extract (5, 25, 50, 100, 150, and 250 mg/kg, i.p.), fluoxetine (10 mg/kg, i.p.), and/or desipramine (50 mg/kg, i.p.) and were sacrificed 30 min later. Brains were removed, homogenized, and centrifuged at 4˚C. The supernatant was used for subsequent neurotransmitter detection by ELISA. Our results indicated that the aqueous extract of saffron (50, 100, 150 and 250 mg/kg, i.p.) increased brain dopamine concentration in a dose-dependent manner compared with saline. In ad- dition, the brain glutamate concentration increased in response to the highest dose of the extract (250 mg/kg, i.p.). In- terestingly, the extract had no effect on brain serotonin or norepinephrine concentration. Our findings show that the aqueous extract of saffron contains an active component that can trigger production of important neurotransmitters in brain, namely, dopamine and glutamate. In addition, these results provide a cellular basis for reports concerning the antidepressant properties of saffron extract in humans and animals. Keywords: Saffron; Glutamate; Dopamine; Norepinepherine; Serotonin 1. Introduction Depression is a common and pernicious illness that can occur at many stages of life. Between 15% and 20% of patients have symptoms that persist for at least 2 years, and often these patients do not fully recover between de- pressive episodes [1]. Depression is also associated with high rates of relapse, recurrence, disability, and death [2]. Collectively, the high rates of chronicity, relapse, recur- rence, morbidity and mortality highlight the importance of safe and effective long-term pharmacological treat- ment of this disease. However, evidence indicates that in- dividuals with depression are seriously undertreated and receive inappropriate or inadequate treatment, with enor- mous costs to individuals and society [1]. Saffron, Crocus sativus L. (Iridaceae), is used in folk medicine as an aphrodisiac and antispasmodic agent, expectorant and antidepressant [3]. Recent studies have demonstrated that saffron extract and its constituent, cro- cin, show interactions with morphine reward properties [4-10]. Interestingly, these studies have shown that the extract may interact with the neural elements located in the shell region of the nucleus accumbens [8]. On the other hand, Hosseinzadeh and Jahanian have shown that the extract and safranal and crocin can reduce the signs of morphine withdrawal syndrome in mice [11]. Che- mical studies on Crocus sativus have shown the presence of constituents such as crocin, crocetin, safranal, and picrocrocin [12]. However, until today, there have been * Corresponding author. Copyright © 2013 SciRes. JBBS