Effects of saffron [Crocus sativus L.] stigma extract and its active constituent crocin on neuropathic pain responses in a rat model of chronic constriction injury

This study was designed to investigate the therapeutic effects of saffron [Crocus Sativus L] and its main constituent crocin on neuropathic pain behavioral responses induced by chronic constriction injury [CCI] in rats. Adult male Wistar rats [200 to 250 g] were randomly assigned into 5 groups: Sham + saline, CCI + saline, CCI+ saffron [30 mg/kg], CCI +crocin [15 mg/kg] and CCI + crocin [30 mg/kg]. CCI was induced by applying 4 loose ligatures around the sciatic nerve. Two weeks after nerve lesion, injections of saline, saffron or crocin were started and continued until 26th day post-surgery. Pain behavioral responses including mechanical allodynia [von Frey filament testing] and thermal hyperalgesia were measured in 14, 17, 20, 23, 26, and 40th days after CCI. CCI significantly increased pain behavioral responses. Saffron and crocin [30 mg/kg] decreased thermal hyperalgesia and mechanical allodynia on day 26, and this effect continued until the day 40. Crocin at lower dose [15 mg/kg] was ineffective. These findings indicate that treatment of saffron and crocin after CCI may have a therapeutic effect against neuropathic pain, suggesting that these substances may offer new strategies for the treatment of this highly debilitating condition

Opiate system mediate the antinociceptive effects of coriandrum sativum in mice

Our previous study showed that Coriandrum sativum [CS] has antinociceptive effects, but the mechanisms that mediate this effect are not clear. The present study was designed to test the role of opiate system in the antinociceptive effects of CS on acute and chronic pain in mice using Hot Plate [HP], Tail Flick [TF] and Formalin [FT] tests and also to compare its effect with dexamethasone [DEX] and stress [ST]. Young adult male albino mice [25-30 g] in 33 groups [n = 8 in each group] were used in this study. CS [125 250, 500 and 1000 mg/Kg IP], DEX [0.5, 1 and 2 mg/Kg IP], vehicle [VEH] or swim stress were used 30 min before the pain evaluation tests. Acute and chronic pain was assessed by HP, TF and FT models. In addition, Naloxone [NAL, 2 mg/Kg, IP] was injected 15 min before the CS extract administration in order to assess the role of opiate system in the antinociception of CS. Results indicated that CS, DEX and ST have analgesic effects [p < 0.01] in comparison with the control group and higher dose of CS was more effective [p < 0.001]. Besides, pretreatment of NAL modulates the antinociceptive effects of CS in all models [p < 0.001]. The above findings showed that CS, DEX and ST have modulator effects on pain. These findings further indicate that the CS extract has more analgesic effects than DEX and ST and also provides the evidence for the existence of an interaction between antinociceptive effects of CS and opiate system

[Effects of acute stress and corticosterone on fear memory extinction in mice]

Memory extinction is the process that being after recalled and actively previously consolidated memories. Although recent studies suggest that acute stress and glucocorticoids have modulatory effects on fear memory extinction, but their effects are not known clearly. The aim of this study was to determine the effects of acute stress and corticosterone on fear memory extinction in passive avoidance task in mice. In this experimental study, 48 male albino mice [25-30 gr] were used, which were trained in one trial inhibitory avoidance task [1mA, 3 s footshock]. Corticosterone [0.5, 1 and 3 mg/kg] was systemically administrated 30 min prior to memory reactivation. In addition, acute stress was induced in some groups using restrainer [plexiglass tube] for 10 min at the same time of cortisterone adminstration. The process of memory extinction was assessed by retention tests given 2, 5, 7 and 9 days after memory reactivation. The latency to re-enter dark compartment of the apparatus was recorded. The results showed that systemic injection of corticosterone [1 or 3 mg/kg] or acute stress facilitates fear-related memory extiction significantly. Our findings indicate that glucocorticoid system and acute stress play an important role in fear memory extiction. Our findings might be helpful to develop therapeutic methods to treat pathological emotional memories such as those seen in post-traumatic disorders and phobia

Effects of Valeriane officinalis, Satureja hortensis and Mentha piperita extracts on the withdrawal syndrome signs in mice

Several studies have demonstrated the antinociceptive, anti-inflammatory, sedative and smooth muscle relaxant activities of the Valeriane Officinalis [VO], Satureja Hortensis [SH], and Mentha Piperita [MP]. The aim of this study was to determine the effects of the aqueous or hydroalcoholic extracts from these plants on morphine withdrawal syndrome signs in mice. 112 male albino mice [25-30 g] were used. Morphine was used to produce drug dependency by Marshall method. Different doses of the aqueous extracts of VO [25, 50, 100 mg/kg] and SH [25, 50, 100, 200 mg/kg IP] and the hydroalcoholic extract of MP [50, 100, 200, 500 mg/kg IP] were injected to morphine-dependent mice 30 min before the naloxone injection [2mg/kg]. Control mice received saline. The severity of the morphine withdrawal responses was estimated by recordeing the number of jumping and the amount of weight feces during 3o min after naloxone injection. The results showed that the extracts of VO [25 mg/kg], SH [200 mg/kg], and MP [all doses] significantly [P<0.05] decreased the number of jumping. Also, the VO [50 and 100 mg/kg], SH and MP [all tested doses] significantly decreased the weight of stool. Our findings indicate that the extracts of VO, SH, and MP may diminish the morphine withdrawal syndrome signs

Antinociceptive effects of hydroalcoholic extract of thymus vulgaris

Previous investigation has shown that Thymus Vulgaris [TV] modulates pain. The aim of this work was to examine the role of TV on acute and chronic pain and compares its effect with dexamethasone [DEX] and stress [ST] by using Hot plate, Tail flick and Formalin tests in mice. In this study male albino mice [25-30 g.] in 21 groups [n = 147] were used. TV [100, 500 and 1000mg/kg], DEX [0.5, 1 and 2 mg/kg] and vehicle [VEH] were injected 30 minutes before pain assessment tests. Stress was applied by 1 min swimming in cold water [18 - 22°]. Acute and chronic pain was assessed by Hot plate, Tail flick and Formalin tests. For assessment of the role of opioid receptors in antinoceception of TV extract, Naloxon [NAL, 2mg/kg, ip] as opioid receptor antagonist was injected before the injection of the more effective dose [500mg/kg] of TV extract. Results indicated that TV, DEX and ST have analgesic effects in all tests [P < 0.01 in comparison with control group]. Above findings showed that TV extract, DEX and ST have modulatory effects on acute and chronic pain. Further research is required to determine the mechanisms by which TV extract has an inhibitory effect on pain sensation

[Influence of basolateral amygdala lesion on the inhibitory effects of propranolol on voluntary exercise- induced enhancement of learning and memory

The beneficial effects of physical activity and exercise on brain functions such as improvement in learning and memory are well documented. In a recent study, we have found that blockade of beta-adrenergic receptors by propranolol attenuates an improvement of learning and memory by exercise. However, the anatomical sites of propranolol actions are not known. The aim of this study was to determine the role of Basolateral amygdala [BLA] in the inhibitory effects of propranolol on the beneficial effects of exercise on learning and memory. In order to block the beta-adrenergic receptors, male mice were received the beta-antagonist propranolol [10 mg/kg], before each night of five consecutive nights of exercise. The BLA lesion was made by electrolytic lesion [2mA, 2 s]. Learning and memory were tested on the Morris water maze task using a two-trials-per-day for five consecutive days. A probe trial was performed two days after the last training day. Our results showed that propranolol reversed the exercise-induced improvement in learning and memory in rat. This effect was not blocked by the BLA lesion. However, lesion of the BLA alone blocked exercise-induced enhancement of learning and memory. These findings indicate beta-adrenergic receptors located outside the BLA may mediate the effects of exercise on learning and memory. Also, the BLA play an important role in the mediating the effects of physical activity on learning and memory

[Effect of hydroalcoholic extract of valeriana officinalis root on the ileum contraction on Guinea pig]

Valeriana Officinalis administrated for treatment of many gastrointestinal disorders traditionally and probably reduced smooth muscle contraction and bowel movement. The aim of this study was to determine the effect of Valeriana Officinalis extract on Ileum contraction of Guinea pig ileum in In Vitro model. This experimental study done on five male Guinea pigs. The animals were sacrificed and the pieces of ileum with 2-3 cm long [at least 6 pieces] dissected and established in normal Tyrod solution plus Carbogen gas in 37°C. Tissue fixed between of two electrodes that connected to stimulator apparatus. The contraction of ileum carried to physiograph by isotonic transducer and recorded. A solution with 5 concentration of Valeriana Officinalis extract was added to the organ bath during ileum stimulation with stimulator and the muscle contraction recorded in 7 responses. Hydroalcoholic extract of Valeriana Officinalis root in concentrations of 5, 15, 50, 150, 500 mg/ml during 0.1 Hz stimulation decreased Ileum contractions in a dose dependent manner. The percent of reduce contraction was 34.45%, 36.07%, 47, 53%, 56.42%, and 76.22% respectively. Also Ec50% of this effect of Valeriana Officinalis was found to be 50 mg/ml [P<0.05]. This study showed that Valeriana Officinalis extracts can decrease ileum contraction in dose dependent manner

[Evaluation the role nitric oxide in corticosterone effect's on anxiety behaviors in mice]

Many evidence indicated that action of glucocorticoid receptors can modulate anxiety behaviors and these effects probably mediated by nitric oxide [NO] system. Thus, in this study, we investigated interaction between corticosterone and NO on anxiety behaviors in mice in elevated plus maze [EPM]. In this experimental study male albino mice [25-30 g] were used. A standard EPM was used to determine anxiety behaviors. Two behavioral measures were used that include of the percentage of time spent in the open arms and the ratio of open arm entries to total entries during 5 min. Animals received IP injection of L-Name 30 mg/kg as an inhibitor or L-Arginine 50 mg/kg as a synthesis of NO or saline 60 min and corticosterone [1, 2.5, 5 mg/kg] 30 min before of evaluation. Analysis of data indicated that corticosterone at doses of 1 and 2.5, but not 5 mg/kg significantly reduced anxiety behavior in mice [P < 0.05]. Also pretreatment of L-Name potentiate but injection of L-Arginine had inhibition of corticosterone effects [P < 0.05]. This study revealed that glucocorticoid induces anxiolytic effects and these effects probably potentiate by NO inhibitor and reduced by NO synthesis. Therefore, it seems that there are interaction between of glucocorticoid and NO system for control of anxiety behaviors

Peripheral injection of dexamethasone modulates anxiety related behaviors in mice: an interaction with opioidergic neurons

Stress and anxiety initiates a cascade of biochemical and endocrine event which results in behavioral and electrophysiological effects in both animals and humans. In this study, we investigated the effects of dexamethasone [DEX], as a synthetic glucocorticoid, and its interaction with opioidergic system on anxiety related behavior in mice. Young adult male mice were used in this study. A standard elevated plus-maze was used to determine anxiety levels in animal. Different doses of DEX [0.1, 0.5, 1, 2 and 10 mg/kg, SC] or vehicle was injected 30 min before of evaluation. Naloxone [1 and 2 mg/kg, IP] was injected 5 min before the DEX [0.5 and 1 mg/kg] administration. Results indicated that DEX at doses of 0.5 and 1 reduced and in dose of 10 mg/kg increased anxiety related behaviors significantly [P < 0.05 in all cases]. Also pretreatment of naloxone at doses of 1 and 2 mg/kg attenuated the effects of lower doses of DEX on anxiety related behaviors. Finding above indicated that peripheral administration of glucoc orticoids induces biphasic effects on anxiety related behaviors: anxiolytic effects in lower doses and anxiogenic effects in a high dose. Data also revealed an involvement of opioidergic system in anxiolytic effects of glucocorticoids