Aims:In the present study, we investigated the possible influence of the opioidergic system of the dorsal hippocampus on anxiety-like behaviors.Methods: Elevated plus-maze, which is one of the methods used for testing anxiety, was used in the present study. Rats were anesthetized with ketamine and xylazine and special cannulas were inserted stereotaxically into the CA1 region of the dorsal hippocampus. After 1 week of recovery, the effects of intra-CA1 administration of morphine (0.25, 0.5, 1 and 2 mg/rat; 1 ml/rat; 0.5 ml/in each side), naloxone (2, 4, 6 and 8 mg/rat), enkephalin (1, 2, 5 and 10 mg/rat) and naltrindole (0.25, 0. ]-enkephalin acetate hydrate into the CA1, induced an anxiolytic-like effect. Furthermore, intra-CA1 injection of d-opioid receptor antagonist, naltrindole hydrochloride, increased anxiety-related behaviors.
Conclusions:The results of the present study demonstrate that activation of m-opioid receptors in this area produce an anxiogenic response while activation of d-opioid receptors produces an anxiolytic response.
Affective disorders including depression and anxiety are among the most prevalent behavioral abnormalities in patients with Alzheimer's disease (AD), which affect the quality of life and progression of the disease. Dysregulation of the hypothalamic-pituitary-adrenal-(HPA) axis has been reported in affective disorders and AD. Recent studies revealed that current antidepressant drugs are not completely effective for treating anxiety- and depression-related disorders in people with dementia. ATP-sensitive-potassium-(K) channels are well-known to be involved in AD pathophysiology, HPA axis function and the pathogenesis of depression and anxiety-related behaviors. Thus, targeting of K channel may be a potential therapeutic strategy in AD. Hence, we investigated the effects of intracerebroventricular injection of Aβ25-35 alone or in combination with glibenclamide, K channel inhibitor on depression- and anxiety-related behaviors as well as HPA axis response to stress in rats. To do this, non-Aβ25-35- and Aβ25-35-treated rats were orally treated with glibenclamide, then the behavioral consequences were assessed using sucrose preference, forced swim, light-dark box and plus maze tests. Stress-induced corticosterone levels following forced swim and plus maze tests were also evaluated as indicative of abnormal HPA-axis-function. Aβ25-35 induced HPA axis hyperreactivity and increased depression- and anxiety-related symptoms in rats. Our results showed that blockade of K channels with glibenclamide decreased depression- and anxiety-related behaviors by normalizing HPA axis activity in Aβ25-35-treated rats. This study provides additional evidence that Aβ administration can induce depression- and anxiety-like symptoms in rodents, and suggests that K channel inhibitors may be a plausible therapeutic strategy for treating affective disorders in AD patients.
Mild traumatic brain injury (mTBI) is a major public health risk for developing anxiety-related disorders and hypothalamus–pituitary–adrenal (HPA) axis dysregulation in humans. Extensive research has shown that dietary intake or supplementation of the natural flavonoid quercetin might be useful for treating anxiety-related symptoms. The objectives of this study were to determine whether quercetin treatment can attenuate anxiogenic-like behaviors and normalize HPA axis function in mice with mTBI. Animals subjected to mTBI were treated daily with quercetin (50 mg/kg) or diazepam (positive control, 3 mg/kg) for 14 days. Four behavioral tests (open field, plus maze, light-dark box, and zero maze) were used to assess anxiety-related behaviors in mice. To evaluate HPA axis function, adrenocorticotropic hormone and corticosterone were measured in the serum of mice after the anxiety tests. Quercetin treatment was found to significantly reduce anxiety-like behaviors in mTBI-induced mice. A strength of this study is the consistency of results among anxiety tests. The dysregulation of the HPA axis in mTBI-induced mice treated with quercetin was also attenuated, with decreased levels of adrenocorticotropic hormone and corticosterone. The effects of quercetin were comparable with those of diazepam treatment. Taken together, these results suggest that quercetin might be useful for treating anxiety-related symptoms and HPA axis hyperreactivity in patients with mTBI.
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