---

Adenosine acts as neuromodulator in the brain, which its involvement in a wide range of brain processes and diseases has been studied, such as epilepsy, sleep, anxiety, panic disorder, Alzheimer’s disease, Parkinson’s disease and schizophrenia. Adenosine receptors have been detected: A1R, A2AR (A2AR), A2BR, and A3R. A1R and A2R inhibit cAMP production, while A2AR and A2BR stimulate cAMP production. These receptors are distributed in various areas of the central nervous system. A2AR is highly expressed in the olfactory bulb, caudate putamen, nucleus accumbens, and tuberculum olfactorium. The function of several receptors such as dopamine D2 receptor (D2R) is influenced by activation of adenosine A2A receptor. Three distinct dopamine projection pathways are formed from the substantia nigra–ventral tegmental area complex. Mesocortical pathway and mesolimbic pathway are known as first and second pathways. Axons project to the striatum, described nigrostriatal pathway known as third pathway. This pathway completes the neural circuits of the basal ganglia responsible for motor control, although recent document also points to a very important role in the motor changes associated with severe depression. Adenosine A2A receptor and D2R are co-localized in the dorsal and ventral striatum and are mutual inhibitors. On one hand, A2AR–D2R heteromers are formed and, when the A2AR is activated, conformational changes are transferred to the D2R. This ultimate to a reduction in D2R recognition and signaling on the other hand, D2R activation inhibits cAMP mediated-effects of A2AR by inhibiting adenylyl-cyclase. Finally, recant study showed that A2AR overexpression is associated with depression, which may describe the depressive signs seen in aging, chronic stress, and Alzheimer’s disease. We hypothesized that changes in expression of A2AR in nigrostriatal system may contribute in creation of depression with motor disorders.

---

Dopamine (DA) is one of the main catecholamines in the brain and is crucial for movement coordination, endocrine function, reward, mood, memory and emotions. The dopaminergic system is the primary therapeutic target in the treatment of Parkinson’s disease (PD), drug addiction and schizophrenia. Notwithstanding, dysfunction of central dopaminergic neurotransmission has also been associated to depression, which has been linked to dysregulation of DA release or alterations in dopamine receptors expression or function. studies in humans indicated that the efficacy of dopamine receptor agonists with high binding affinity to D3R compared to D2R, including aripiprazole, cariprazine and pramipexole, a drug commonly used for the treatment of motor symptoms in PD but also effective for the treatment of major depression. Furthermore, reduction of DA release at synapses leads to increased D2R/D3R binding in temporal cortex of depressive patients. Similarly, the treatment of animal models with antidepressant drugs increase the density of D2R/D3R binding sites in the nucleus accumbens without altering the density of binding sites for D1-like receptor. Interestingly, expression of D3R significantly increased in the shell of nucleus accumbens, when is used chronic administration of classical antidepressants and repeated electroconvulsive therapy in rats. This data suggested that D3R may play an important role in the pathophysiology of depression.

---

The mesolimbic dopamine (DA) system contains both D1-like and D2-like receptors, has been connected to control of locomotor behavior. An apparent role for D1 and D2 receptors throughout the mesolimbic system in the alteration of locomotor behavior has been demonstrated in pharmacological studies. The nucleus accumbens (NAc) is comprised of a core and a shell subregion, which is a component of the mesolimbic DA system, and has been specifically implicated in locomotor behavior. Intra-NAc injections of D1 and D2 agonists have been found to increase locomotor activity. The DA system also plays a role in regulating anxiety-like and fear behavior. Pharmacological studies have shown that D1 and D2 receptors are involved in anxiety-like behavior. Findings seem to be dictated by a number of factors, including strain, route of administration, ligand selected and behavioral test. Fear behavior may often be indiscernible from anxiety-like behavior in animal models though the anatomical aspects may be different. Fear cues have been shown to decrease DA transmission in the NAc core, but increase transmission in the shell. Dopamine release in the NAc also appears to assist in encoding cues that predict punishment avoidance. These data suggest a role between fear and DA transmission and suggest that there may also be a role of accumbal DA in anxiety-like behavior.

---

Anxiety is one of the most common symptoms of mental disorders, significantly affecting work function and interpersonal relationships. Its characteristics include a set of cognitive, physical, emotional and behavioral-symptoms. Some of these symptoms are: feeling empty heart, shortness of breath, palpitations, flushing, excessive sweating, numbness, dizziness and shaking hands. Given the high prevalence of these symptoms and their significant impacts on the function of individuals, it is necessary to take fundamental steps for tackling with the raised issues. Commonly used medication for anxiety disorders has its own side effects therefore, many studies have been conducted to find effective drugs with fewer side effects. Currently, the use of medicinal plants is progressing due to relying on the beliefs of a certain region people, fewer side effects and being cost-effective. The aim of this study was to review anti-anxiety and sedative effectiveness of some medicinal plants used in traditional medicine of Iran. This study is of review article type. Psychology and medical journals were searched for anxiety keyword and the related papers published in the years between 2000 and 2014 were reviewed. The results of literature review revealed that extract of Portulaca Oleracea L, gum of Pistacia Vera L, Nardostachys Jatamansi, Achillea Millefolium, Rosa Damascene, extract of fenugreek, extract of Cassia Fistula, Feniculum Vulgare and Silybum Marianum have anti-anxiety effects. In addition, there were no significant differences in anxiolytic effects between Citrus Aurantium and diazepam and Passiflora Caerulea and oxazepam.