Research Article EVALUATION OF ANTIDEPRESSANT ACTIVITY OF DIPHENHYDRAMINE IN MICE GHADA A. TAQA Mosul University, College of Dental, DBS DEPT IRAQ, Email: amertaqa@hotmail.com Received: 15 August 2013, Revised and Accepted:16 August 2013 ABSTRACT The study aims to evaluate the antidepressant activity of different doses of diphenhydramine in mice at (0.5, 1, 2 mg /Kg, IP). Materials and Methods: The mice were divided into 5 groups for each testing methods, each group consist of five animals. Group 1 served as a control and was given normal saline 0.9% (5ml/kg,IP), group 2 received (20 mg /Kg, IP) fluoxetine as a standard control. Group 3, 4, 5 were treated with three different doses of diphenhydramine (0.5, 1, 2 mg /Kg, IP) respectively. The normal behaviors of each group of mice were evaluated after 30 min. of drug administration. The test was used to evaluate the antidepressant activity of diphenhydramine in Open Field, Modified Forced Swimming Test and Tail Suspension Test Results: It is found that the increase in the locomotor activity in open field cage by increasing the number of square cross to (94.2±28.7) (93.2±25.6) (86.6±22.1) respectively according to the doses of diphenhydramine in comparison with control group (69.4±27.2) at p< 0.05. In modified forced swimming test, the result also showed that the administration of diphenhydramine at (0.5, 1, 2 mg /Kg, IP) were reduced the immobility time (68.8 ± 21.1) (56.4 ± 17.7) (47.6 ± 21.7) Sec. respectively in comparison with control group. In the present study, It is found that the administration of diphenhydramine at (0.5, 1, 2 mg /Kg,IP) were significantly increased in the swimming time (143.2 ± 16.2) (152.6 ± 18.7) (160.02 ± 15.5) Sec. Sec. in comparison with control group (28.8 ± 3.4) Sec. Conclusion: Thus, this study suggested that the administration of diphenhydramine is produced a good therapy used in the treatment of depressed patients without side effect . Keywords: Antidepressant, Tail suspended test, Open failed test, Diphenhydramine, Force swimming test. INTRODUCTION Depression is a serious mood disorder that affect of most population nowadays (Yagiela et al., 2011). The main symptoms of depression are due to functional deficiency in the levels of monoaminergic transmitters’ noradrenalin, 5- hydroxytriptamine and dopamine in the brain (Harvey et al 2012). Drugs that increase the level of these neurotransmitters in the CNS showed antidepressant activity (Meyers 2000). The major antidepressant therapies aim to increase the synaptic concentration of serotonin or norepinephrine or both and thus normalize the neurotransmission (Jithan and Chinnalalaiah, 2009). Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for the treatment of depression and several anxiety, the actions of SSRIs at disorder (David et al., 2009). In the past decayed, we found drugs that inhibit reuptake of the neurotransmitter serotonin have antidepressant activity therefore increase the search for viable of antidepressant drugs with fewer side effects (Domino and Edward, 1999). Diphenhydramine is a first generation H1 antihistamine. It the oldest H1 antihistaminergic drug used clinically for the treatment of many conditions such as common cold, anaphylaxis, pruritus and Parkinsonism disease (Raphael et al., 2006). Diphenhydramine is an H1receptor antagonist receptor; these receptors are found in most part of the body such as smooth muscles, vascular endothelial cells, heart tissues, and the central nervous system (Yagiela et al., 2004). Histamine is considered as central neurotransmitters because it is have many criteria for a neurotransmitter substance (Montoro et al., 2006). Brain histamine is suggested to have physiological role in thermoregulation, body fluid balance, sleep and wakefulness (Barbier and Bradbury 2007) and release of certain hormones (Bealer and Crowley, 1999). Brain histamine appears to play some biological roles in control of mood, locomotor activity, emotion and other behavioral functions (Leza et al, 1991, Browen et al , 2001 ). Histamine exist in both peripheral and central system therefore the disturbance in central histamine neuronal system may be considered as an one of behavior disorders because If histamine is found in high levels, the patients are depressed, but low histamine levels are causes nervous, anxious and paranoid (Prousky et al 2002). This action of histamine in neuronal system might be responsible on pathophysiology of depression and therefore used drugs that modulation of central histamine neuronal system may be useful in the treatment of depression (Kano et al, 2004). The goals of the present investigation were undertaken to evaluate the antidepressant effect of different doses of diphenhydramine in mice as a model of an depressive state induced by (tail suspended test, swimming test, open field test) and the ability to treat depression without adverse effects. MATERIALS AND METHODS Animals Healthy albino mice of either sex weighing 25-30 gm were selected for the study. The animals were housed under laboratory condition, at temperature 22± 2 °C with a natural light \ dark cycle and fed with standard diet. The animals were transferred to the laboratory environment for at least one hour before used. Each animal was used only one and received only one dose of the drugs tested. Animals were obtained from animal care house in Dentistry Collage /Mosul University/ Iraq. Experimental design The drugs used in this Experiment were Diphenhydramine (NDI- IRAQ), Fluoxetine. Diphenhydramine and fluoxetine were dissolved in normal saline. All drugs were administered intraperitoneally (IP) in a volume 5ml\kg body weight. The mice were divided into 5 groups for each testing methods, each group consist of five animals. Group 1 served as a control and was given normal saline 0.9% (5ml/kg, IP), group 2 received (20 mg /Kg, IP) fluoxetine as a standard control. Group 3, 4, 5 were treated with three different doses of diphenhydramine (0.5, 1, 2 mg /Kg, IP) respectively. The Vol 1, Issue 2 , 2013 ISSN-2321-4406