The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review

The neurobiology and control of anxious states

Glucagon-like peptide-1 (GLP-1) is a gut peptide that, together with its receptor, GLP-1R, is expressed in the brain. Here we show that intracerebroventricular (i.c.v.) GLP-1 and [Ser(2)]exendin(1-9) (HSEGTFTSD; homologous to a conserved domain in the glucagon/GLP-1 family) enhance associative and spatial learning through GLP-1R. [Ser(2)]exendin(1-9), but not GLP-1, is also active when administered peripherally. GLP-1R-deficient mice have a phenotype characterized by a learning deficit that is restored after hippocampal Glp1r gene transfer. In addition, rats overexpressing GLP-1R in the hippocampus show improved learning and memory. GLP-1R-deficient mice also have enhanced seizure severity and neuronal injury after kainate administration, with an intermediate phenotype in heterozygotes and phenotypic correction after Glp1r gene transfer in hippocampal somatic cells. Systemic administration of [Ser(2)]exendin(1-9) in wild-type animals prevents kainate-induced apoptosis of hippocampal neurons. Brain GLP-1R represents a promising new target for both cognitive-enhancing and neuroprotective agents.

Glucagon-like peptide-1 receptor is involved in learning and neuroprotection

OBJECTIVE: The objective of this paper is to review the literature regarding Withania somnifera (ashwagandha, WS) a commonly used herb in Ayurvedic medicine. Specifically, the literature was reviewed for articles pertaining to chemical properties, therapeutic benefits, and toxicity. DESIGN: This review is in a narrative format and consists of all publications relevant to ashwagandha that were identified by the authors through a systematic search of major computerized medical databases; no statistical pooling of results or evaluation of the quality of the studies was performed due to the widely different methods employed by each study. RESULTS: Studies indicate ashwagandha possesses anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory, hemopoetic, and rejuvenating properties. It also appears to exert a positive influence on the endocrine, cardiopulmonary, and central nervous systems. The mechanisms of action for these properties are not fully understood. Toxicity studies reveal that ashwagandha appears to be a safe compound. CONCLUSION: Preliminary studies have found various constituents of ashwagandha exhibit a variety of therapeutic effects with little or no associated toxicity. These results are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using ashwagandha for a variety of conditions should also be conducted. (Altern Med Rev 2000;5(4) 334-346)

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Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review.

https://bernirey80.files.wordpress.com/2007/05/file_se_2003.pdf

A review of 25 years of the social interaction test.

Two new glycowithanolides, sitoindoside IX (1) and sitoindoside X (2), isolated from Withania somnifera Dun., were evaluated for their immunomodulatory and CNS effects (anti-stress, memory and learning) in laboratory animals, because the plant extract is used by practitioners of the Indian systems of medicine for similar purposes. The two compounds, in doses of 100–400 μg/mouse, produced statistically significant mobilization and activation of peritoneal macrophages, phagocytosis and increased activity of the lysosomal enzymes secreted by the activated macrophages. Both these compounds (50–200 mg/kg p.o.) also produced significant anti-stress activity in albino mice and rats and augmented learning acquisition and memory retention in both young and old rats. These findings are consistent with the use of W. somnifera, in Ayurveda, to attenuate cerebral function deficits in the geriatric population and to provide non-specific host defence.

Immunomodulatory and CNS effects of sitoindosides IX and X, two new glycowithanolides from Withania somnifera

The anxiolytic activity of diazepam (DZP) (0.25–1 mg/kg) was investigated in streptozotocin (STZ)-induced diabetic adult Charles Foster albino rats of either sex. Diabetes was induced by injecting STZ IP (50 mg/kg; in citrate buffer, pH 4.5). Experiments were performed 72 h later. The rats were subjected to various anxiety paradigms, including the open-field exploratory behaviour, elevated plus maze and elevated zero maze behaviours and the social interaction tests. In addition, rat brain tribulin activity was also assessed as a biochemical marker of anxiety. The results indicate that diabetic rats showed significantly more anxiogenic activity in comparison to non-diabetic rats on open-field, elevated plus maze, zero maze and social interaction tests. In diabetic rats, brain tribulin activity (MAO-A inhibitory component) was significantly increased. DZP dose dependently produced anxiolytic activity on the various behavioural parameters in non-diabetic rats. DZP (0.5 and 1 mg/kg) partially reversed the anxiogenic behaviour of STZ diabetic rats in elevated plus maze and zero maze tests. However, in open field behaviour and social interaction tests significant anxiolytic activity was observed only at a higher dose of DZP (1 mg/kg). The findings indicate that STZ-induced diabetic rats exhibited augmented anxiety on various experimental paradigms and that the anxiolytic effect of diazepam was less marked in diabetic rats as compared to their euglycaemic counterparts.

Differential effects of diazepam on anxiety in streptozotocin induced diabetic and non-diabetic rats

Putative anxiolytic activity of leaf extract of A. indica, was investigated and compared with that of diazepam in rats using elevated plus maze and open field behaviour test paradigms of anxiety. Doses (10, 20, 50, 100, 200, 400 and 800 mg/kg) of freshly prepared leaf extract of A. indica and diazepam (1 mg/kg) were administered (po) once, 45 min prior to behavioural testing. Low doses (10, 20, 50, 100 and 200 mg/kg) of A. indica leaf extract produced significant antianxiety effects both in plus maze and open field test. However, the higher doses of leaf extract (400 and 800 mg/kg) did not show anxiolytic activity. The effects induced by low doses (10, 20, 50, 100, 200 mg/kg) of extract were comparable to those of induced by diazepam (1 mg/kg).

Anxiolytic activity of Azadirachta indica leaf extract in rats.

Shilajit, a panacea of oriental medicine, collected from different countries, exhibits overtly different levels of bioactivity. The effects of shilajit, collected from India, Nepal, Pakistan and Soviet Russia, and the effects of organic constituents isolated from a potent shilajit sample, were studied in a number of antistress and CNS activity paradigms. Shilajit from Kumaon (India), Dolpa (Nepal), and a combintion (1:1) of the total ethylacetate extracts (TE) and fulvic acids (FAs), from Kumaon shilajit, produced statistically significant effects in forced swimming-induced immobility in albino mice; restraint stress and aspirin-induced gastric ulcers in pylorus ligated albino rats; and augmented the learning acquisition and memory retention in old rats. The potential risk of ingesting shilajit, in the native form as a ‘health product’, was appraised in view of its high stable free radical content and possible contamination with mycotoxin-producing fungi. Hence, there is an imperative need for formulation of shilajit on the basis of its isolated active constituents (TE and FAs). Additionally, the physical and spectral characteristics of active FAs (bioactivity-directed) were determined and compared with those of less active and inactive samples. These would provide predictability for selection of FAs for formulation of shilajit.

The need for formulation of Shilajit by its isolated active constituents

Piracetam, a prototype of a new class of psychotropic agents, the nootropic agents, which improve learning ability and memory retention, was found to induce a dose-related prevention of disruption of acquisition of a passive avoidance response produced by electroshock application. The amnesia attenuating effect of piracetam was accompanied by prevention of the decrease in acetylcholine concentrations of rat brain induced by electroshock. The study indicates that the cognition enhancing effect of piracetam may be due to a facilitatory effect on cholinergic transmission.

Jaiswal Ak

Papers

Immunomodulatory and CNS effects of sitoindosides IX and X, two new glycowithanolides from Withania somnifera

Differential effects of diazepam on anxiety in streptozotocin induced diabetic and non-diabetic rats

Anxiolytic activity of Azadirachta indica leaf extract in rats.

The need for formulation of Shilajit by its isolated active constituents

Effect of piracetam on electroshock induced amnesia and decrease in brain acetylcholine in rats.