Involvement of GABAergic system in regulation of the anxiolytic- and antidepressant-like effects of Scrophularia striata extract in rats.

CONTEXT: Neuropsychiatric disorders, like anxiety and depression, are global problems for clinical researchers in neurology. Recently, some authors have shown neuroprotective and anti-inflammatory effects of Scrophularia striata Boiss (Scrophulariaceae) extract in rodents. OBJECTIVE: The purpose of the current study was to investigate the effects of S. striata extract on anxiety and depressant-like behaviors and find a possible mechanism for these impacts. MATERIALS AND METHODS: In this study, the elevated plus-maze (EPM) and forced swimming test (FST), which are useful models for selective identification of anxiolytic and antidepressant drug effects in rodents, were used. We investigated the effects of S. striata ethanol extract at different doses (20, 50, 100, 160 and 220 mg/kg) on anxiety and depression behaviors in the EPM and FST, and then we assessed the role of γ-aminobutyric acid (GABA)A receptor in modulation of the effects of S. striata extract in the brain. RESULTS: Our results showed that effective doses of S. striata (100 and 160 mg/kg) increased the percentages of open arm time and entries in the EPM and decreased immobility time in the FST in comparison with control group, indicating anxiolytic and antidepressant effects, respectively. Moreover, intracerebroventricular administration of GABAA receptor agonist (muscimol; 1 µg/rat) enhanced the impact of S. striata, and GABAA receptor antagonist (bicuculline; 1 µg/rat) blocked these effects in rats, indicating that significant interactions existed between S. striata and the GABAergic system in the brain. DISCUSSION AND CONCLUSION: Findings of this study suggest that anxiolytic and antidepressant effects of S. striata may be modulated via the GABAergic system.

Fluoxetine normalizes the effects of prenatal maternal stress on depression- and anxiety-like behaviors in mouse dams and male offspring.

Maternal depression during pregnancy and the postpartum period (lactation) is a common debilitating condition affecting mother-fetus/-infant interactions, which can be a risk factor for cognitive and affective disorders in mothers and their children. Selective-serotonin-reuptake-inhibitor-(SSRI) pharmacotherapy is known as the first-line treatment of maternal depression. However, its use during pregnancy and lactation is a topic of concern. The present study aimed to investigate the effects of prenatal stress alone or in combination with fluoxetine (FLX) on hypothalamic-pituitary-adrenal axis (HPA) activity, anxiety-/depression-like behaviors in dams and in offspring. To do this, gestationally-stressed and non-stressed mouse dams were orally treated with FLX-(8/mg/kg/day) from gestational day 10 to lactation day 20. The behavioral outcomes of prenatal stress and FLX treatment in dams and male offspring were assessed using the sucrose preference, forced swim, zero maze, and light-dark box tests. Stress-induced corticosterone levels were also evaluated as indicative of abnormal HPA-axis function. Our findings indicated that maternal stress resulted in increased depression-like behavior and HPA axis hyperactivity in dams during pregnancy and lactation which were reversed by FLX. Furthermore, prenatal stress increased anxiety/depression-like behaviors and HPA-axis reactivity in male offspring. These effects were reversed by maternal FLX treatment. Developmental FLX exposure, without prenatal stress, did not have any adverse effects on the above measured parameters. Our results suggest that prenatal stress induces maternal depression-like behavior which affects the development of affective symptoms in male offspring, and that remediation of maternal depression-like behavior coincidences with the normalization of anxiety-and depression-like symptoms in male offspring.

Possible Modulation of the Anexiogenic Effects of Vitex Agnus-castus by the Serotonergic System.

OBJECTIVES: There is well documented evidence for the increase in widespread use of complementary and alternative medicine in the treatment of physical and psychiatric symptoms and disorders within the populations. In the present study, we investigated the influence of V itex agnus-castus (vitex) on anxiety-like behaviors of rats. MATERIALS AND METHODS: Elevated plus maze which is one of the methods used for testing anxiety is used in our present study. Rats were orally administrated with vitex for two week. The anxiety test was carried out after two weeks of oral administration of vitex. For evaluating interaction of vitex and serotonergic systems, rats were anaesthetized with ketamine and special cannulas were inserted stereotaxically into the third ventricle (TV) of brain. After 1 week recovery, the effects of serotonegic agents on anxiety were studied. RESULTS: Oral administration of vitex (100, 200, 300 mg/kg) for two weeks induced an anxiogenic-like effect which was shown through specific decreases in the percentages of open arm time (OAT %) and open arm entries (OAE %). Intra - TV infusion of 5HT1A receptor agonist, 8-OH-DPAT (5, 10 and 25 ng/rat) increased OAT% and OAE%, indicating anxiolytic-like behavior. However, injection of 5HT1A receptor antagonist NAN190 (0.25, 0.5 and 1 µg/rat) produced anxiogenic-like behavior. The most effective dose of 8-OH-DPAT (10 ng/rat), when co-administered with vitex (100, 200, 300 mg/kg), attenuated the anxiogenic-like effects of vitex significantly. Injection of the less effective dose of NAN190 (0.5 µg/rat), in combination with vitex (100, 200, 300 mg/kg), potentiate anxiogenic effects of vitex. CONCLUSIONS: These results illustrate that 5HT1A receptor is involved in the anxiogenic effects of vitex.