Behavioral and biochemical characterization of elevated “I-maze” as animal model of anxiety

AbstractThe elevated I-maze is a modification of the elevated plus-maze model of anxiety in mice. The design of I-maze comprises a straight wooden passage, resembling the English letter “I,” divided equally into three areas; two enclosed areas (close arms) at both ends of the “maze” and an open area in the center of two enclosed areas. The I-maze completely avoids the central platform of elevated plus-maze, removing any ambiguity in time spent on central platform and allowing uninterrupted animal exploration. In this model, diazepam (1 mg/kg) and gabapentin (10 mg/kg) significantly increased the percentage of time spent in the open areas (%TO) and the number of unprotected head dips (uHDIPS), and reduced the number of protected head dips (pHDIPS) and stretch attend postures (SAP) from close to open arm. Similarly, fluoxetine (5 mg/kg) significantly increased %TO and uHDIPS, and significantly decreased SAP from close to open arm, but it did not have any significant effect on pHDIPS. The 5-HT3 receptor antagonist, ondansetron (0.1 mg/kg), did not produce any significant change in all the behaviors, observed, as compared to vehicle-treated control mice. On the other hand, the anxiogenic agent, caffeine (15 mg/kg), did produce a significant decrease in %TO and uHDIPS, and significantly increased pHDIPS and SAP from close to open arm. Mice confined in open area of I-maze bring the relevant biochemical changes associated with anxiety behavior, showing significant increase in the levels of plasma nitrate and plasma corticosterone. These data indicate that a combination of novel design of elevated I-maze and a detailed behavioral analysis provides a sensitive model for the measurement of anxiety

ATTENUATION OF ANTINOCICEPTIVE EFFECT OF MORPHINE IN DIABETIC MICE: NITRIC OXIDE OR INTERLEUKIN-2

Objective: The present study was designed to explore the mechanistic role of interleukin-2 in diabetes-induced decrease in the antinociceptive effect of morphine in mice. Role of interleukin-2 was investigated by employing cyclosporin, a interleukin-2 synthesis inhibitor. Methods: Diabetes was induced in mice by single intra peritoneal injection of Streptozotocin (200 mg/kg, i. p.). Nociceptive threshold in diabetic mice was measured by Rodent tail-flick test. Nitrite levels in the urine of mice were estimated by employing Greiss reagent. Results: A significant decrease in antinociceptive effect of morphine was observed in mice. Administration of cyclosporin (20 mg/kg, s. c., b. d.) in diabetic mice significantly increased antinociceptive effect of morphine in diabetic mice. However, administration of cyclosporin (20 mg/kg, s. c., b. d.) failed to significantly change the increased nitrite levels in diabetic mice.Conclusion: The present study indicates that interleukin-2 may be responsible for decrease in antinociceptive effect of cyclosporine. The study also indicates that the increase in levels of interleukin-2 is independent of an increase in nitrite levels. It may, therefore, be concluded that nitric oxide has no role in nociceptive changes made by interekin-2 in diabetic mice. Â

A NOVEL NON–RECEPTOR AND NON- GABAERGIC ANTIANXIETY-LIKE ACTIVITY OF FORSKOLIN: SYNERGY WITH DIAZEPAM

Objective: Clinical problems associated with the benzodiazepines like dependence, withdrawal or tolerance may lead to under use of substances based on gamma-amino butyric acid (GABA). Non-GABAergic and substances that elevate cyclic adenosine monophosphate (cAMP) have shown anti-anxiety activity. Therefore, present investigation aimed to explore a non-GABAergic mechanism and non-receptor mediated anti-anxiety activity of a cAMP elevating agent, forskolin.Methods: Elevated plus maze and light/dark box were employed to measure effect of forskolin on anxiety and the noted activity was compared with that of diazepam. cAMP levels were also measured in plasma of mice.Results: Forskolin produced a significant antianxiety- like activity in unstressed mice and stressed mice. Diazepam produced a significant antianxiety- like activity in unstressed mice but not in stressed mice. The noted antianxiety activity of forskolin was accompanied by a significant elevation of cAMP levels.Conclusions: The present findings contribute to suggest a non– receptor mediated anti-anxiety action of a forskolin, acting through cAMP elevation, thus avoiding receptor-mediated adverse effect profile of the conventional anxiolytics.Â

NON – RECEPTOR MEDIATED ANXIOLYSIS BY AMINO GUANIDINE: A NOVEL ACTIVITY AND SYNERGY WITH DIAZEPAM UNDER STRESSED CONDITIONS

 Objective: A novel non-receptor mediated anxiolytic activity of amino guanidine (AG; 50 mg/kg, i.p.) was investigated and its possible interactionwith diazepam (DZP) (2 mg/kg, i.p.) was explored in mice.Methods: Elevated plus maze and light/dark box were used to measure anxiety in Swiss albino mice. Plasma nitrite levels were estimated using Griessreagent to observe the biochemical regulation of mice behavior.Results: AG (50 mg/kg, i.p.) produced a significant antianxiety-like activity and significantly attenuated the plasma nitrite levels in stressed mice.On the other hand, AG (50 mg/kg, i.p.) neither produced a significant antianxiety-like activity nor significantly altered the plasma nitrite levels inunstressed mice. DZP (2 mg/kg, i.p.) produced a significant antianxiety-like activity in unstressed mice but not in stressed mice. DZP (2 mg/kg, i.p.)did not significantly affect plasma nitrite levels in unstressed or stressed mice. AG and DZP, administered together produced a significant antianxietylikeactivity in unstressed and stressed mice. However, combination of AG and DZP significantly attenuated the plasma nitrite levels in stressed micebut not in unstressed mice.Conclusion: These findings suggest a usefulness of a non-GABAergic mechanism of a potential anti-anxiety chemical that may avoid receptor-linkedundesired effects as in case of DZP and may be used with DZP under stressed conditions to serve the reduction of dosage of DZP.Keywords: Amino guanidine, Anxiety, Diazepam, Stress

A Review on Antianxiety Plants

476-483Anxiety is a psychological disorder characterized by a persistent and disproportionate fear unrelated to any genuine risk. Apart from very few chemical remedies available like benzodiazepines and serotonin modulators, not much treatment options are at hand that could safely and effectively alleviate anxiety. The present paper discusses anti-anxiety potential of 56 plants with emphasis on their pre-clinical and clinical reports. Majority of these plants have been found to be acting through modulation of serotonin and -amino butyric acid (GABA) neurotransmitters

Differential effects of nitric oxide synthase inhibitors on anxiety in unstressed and stressed mice

365-372Effects of selective nitric oxide synthase (NOS) inhibitors, 7-nitroindazole (7-NI), a selective inhibitor of neuronal nitric oxide synthase (nNOS) and aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS) on anxiety in unstressed and stressed mice were investigated using elevated plus maze (EPM) test and light-dark test (LDT). 7-NI (20 and 40 mg/kg, ip) produced anti-anxiety effect in unstressed mice but not in stressed mice. AG (50 and 100 mg/kg, ip) produced anxiolytic effect in stressed mice and failed to produce the similar effect in unstressed mice. Nitrite levels were increased in stressed mice, but not in unstressed mice, exposed to EPM and LDT for 5 min. Increased nitrite levels in stressed mice were attenuated by AG, but not by 7-NI. The effects of AG were enhanced by pyrrolidine-dithio-carbamate (PDTC), an inhibitor of NF-κB induction, in stressed mice. The results suggest the possible role of inducible nitric oxide synthase in stress-induced anxiogenesis as compared to unstressed mice, where neuronal form of NOS may plays pre-dominant role

Involvement of p38 MAPkinase in attenuation of antinociceptive effect of morphine in diabetic mice

654-656Experimental diabetes induced by streptozotocin (200 mg/kg, ip) markedly decreased the antinociceptive effect of morphine and significantly increased the urinary nitrite concentration. Administration of FR-167653 (a selective p38MAPKinase inhibitor) in a dose of 4 mg/kg improved the antinociceptive effect of morphine and attenuated the increase in urinary nitrite concentration in diabetic mice. It may be concluded that diabetes-induced decrease in antinociceptive effect of morphine may be due to induction of p38 MAPKinase activity