The role of opioid receptor and voltage dependent calcium channels on the kindling induced by the convulsant pentylenetetrazole (PTZ) were investigated in the rats. Experiment involved 24 rats which were divided into four groups. Kindling was established with PTZ in subconvulsive dose (37.5 mg/kg i.p.) every 48 h and effects were observed within 20 min using five-point scoring system. All animals were kindled to three consecutive-stage five seizures and their stability was tested. Saline, verapamil (calcium channel blocker), naloxone (opioid antagonist) or both of them were then administrated 20 min before PTZ application. Convulsant parameters were significantly (P<0.05) reduced by verapamil. Naloxone had no significant effect on the seizure expression of fully kindled animals, whereas simultaneous application of naloxone and verapamil had profound inhibitory effect on all seizure parameters. The results of the present study suggest that NALOXANE increased the inhibitory effect of verapamil on the seizure induced by PTZ kindling.

The aqueous-ethanol extract of the Hypericum perforatum (Hp-Ext.) was studied for its possible effect on Naloxone (NLX)-precipitated Opium withdrawal physical signs in rats. Purified Opium was used to induce dependence in rats using 8 days treatment schedule. The animals received Opium extract orally twice daily at 09:00 hrs and 19:00 hrs starting with initial dose of 80 mg/kg (equivalent to 8 mg/kg morphine) and increasing to 650 mg/kg (equivalent to 65 mg/kg morphine). Withdrawal syndrome was precipitated with NLX (0.25 mg/kg, s/c). Animals were divided into three groups each containing nine rats. Group one served as a control and received opium + saline during opium dependence schedule and the remaining two groups were treatment group, one of which received Hp-Ext (20 mg/kg, p/o) one hour before NLX induced withdrawal and was administered opium + saline through out the dependence protocol and 2nd treated group received opium along with Hp-Ext doses though out the dependence protocol. The spasmolytic and calcium antagonist activities of the plant extract were studied using isolated tissue experiments suspended in the Krebs solution maintained at 37 ?C and aerated with carbogen gas. The results showed a significant decrease in both, NLX-induced Opium withdrawal Jumps and Wet Dog Shakes behavior in chronically treated group (ANOVA; P < 0.05 followed by Dunnet post hoc analysis) but no significant effect was found in the acute treatment group. Interestingly, a significant effect was observed on diarrhea in acute treatment group (ANOVA; p < 0.05, followed by Student Newman Keuls test) but no such effect was seen in the chronically treated group. In a separate study, the plant extract inhibited K+-induced contractions in isolated rabbit jejunum and trachea preparations thus showing spasmolytic effect mediated through calcium antagonist activity. In view of the reported fact that NLX-induced opioid withdrawal signs could be inhibited by calcium antagonists, our results indicate the possibility that the opioid withdrawal ameliorating effect of H. perforatum extract may be at least partly though calcium channel blockade. Acknowledgements: We gratefully acknowledge the help and cooperation for the supply of Opium by Anti Narcotic Force (ANF) Peshawar Division. Financial support of University of Pehsawar is also acknowledged.

The role of stress in the pathogenesis of ovarian cysts is believed to be mediated by the discharge of endogenous cortisol, which inhibits LH release. Endogenous opioid peptides are involved in many responses to stress. Therefore, the aim of this study was to determine the effect of epidural administration of Naloxone (NX) on cystic regression and follicle development leading to normal oestrus in dairy cattle. This study was conducted on 91 dairy cattle affected by follicular cysts, divided randomly into 3 groups.Group1 (n=30) cows were treated epidurally (lumbo-sacral) with 0.8 mg Naloxan hydrochloride (NX). Group2 (n=30) cows were treated epidurally with GnRH analogue (100 mcg gondorelin acetate). Group3 (n=31) cows were considered as control and received 5 ml normal saline epidurally. Although the results of this study showed that NALOXANE was better than the other two groups to treat follicular cysts, there was no significant difference in differnnt criteria, such as CL formation, increasing plasma P4 concentrations and 1st service conception rates among 3 groups.

Background: There is growing evidence indicating that neuronal calcium channels play an important role in the mechanism of Morphine dependence.Objective: To investigate the acute and long-term effects of Verapamil in Morphine dependent mice. Methods: Mice were rendered dependent on Morphine by subcutaneous injection of Morphine over a period of 5 days. The effects of acute and chronic administration of phenylalkylamine calcium channel antagonist, Verapamil, on Naloxone induced Morphine withdrawal signs was investigated.Results: A single injection of Verapamil proved to be effective in inhibiting some signs of Morphine withdrawal but ineffective in changing the number of jumps. The concurrent injections of Verapamil with Morphine prevented most signs of Morphine withdrawal.Conclusion: The results confirmed the crucial role of voltage-sensitive calcium channels in the adaptations that occur after long-term treatment with Morphine. Concurrent injections of Verapamil with Morphine could be used to prevent some signs of Morphine withdrawal.

Background: Punica granatum Linn. (PG) is native to the Mediterranean region. Its flower exhibited antioxidant activity. The present study attempt to investigate the effect of these extract on uterine contraction and its possible mechanism (s).Methods: Thirty five female Wistar rats (200-300 g) at estrous phases of cycle was examined in this study, pieces of virgin adult rat uterus (1.5cm) were suspended in an organ bath containing 10ml of De Jalon solution at 29oC. Tissue contractility was isometric ally recorded. KCl (60mM), BaCl2 (4 mM) and oxytocin (10 mU/ml) were applied to the tissue in the presence and absence of aqueous and hydroalcoholic extracts of the plant (0.05, 0.1, 0.2, 0.4 and 0.8 mg/ml). Propranolol (1 mM) and NALOXANE (1mM) were added in KCl induced contractions. The results were analyzed by ANOVA and p<0.05 were considered as significant.Results: Cumulative concentration of extracts reduced uterine contractions induced by KCl dose-dependently (p<0.01). Extracts in a dose dependent (p<0.05) reduced uterine contractions decreased dose-dependently after of addition oxytocin. The extracts added cumulatively to the organ bath reduced contractions but they did not affect uterine contractions induced by BaCl2 except the last dose. Spasmolytic effects of the extracts were not affected by propranolol or NALOXANE in KCl induced contractions.Conclusion: Extracts diminished K+-induced contraction in uterus, therefore it seems that substances that decrease K+-induced contraction can also block voltage dependent calcium channel. The extracts did not have any effect on b-adrenoceptors or potassium channels.

Ziziphora tenuior has been used in Iranian folk medicine as an analgesic and for treament of digestive diseases. This study was designed to investigate the antinociceptive effects of hydroalcoholic extract of Z. tenuior on visceral pain and its possible involvement in opioidergic and serotoninergic systems in male albino N-MRI mice. Antinociceptive effect of was determined by writhing test as a model of visceral pain. Z. tenuior extract was administered intraperitonealy (ip) in doses of 50, 75 and 100 mg/kg and antinociceptive effects were compared with indomethacin (5mg/kg, i.p.) and control groups. the most effective dose of the extract was selected for the possible involvement of opioidergic and serotoninergic systems.15 minutes before administration of the effective dose, animals were studied by pretreatment of opioid antagonist, NALOXANE (2mg/kg, i.p.) and serotoninergic antagonist, cyproheptadine (4mg/kg, i.p.) using writhing test. the results of this study showed that hydroalcoholic extract of z. tenuior at 50, 75 and 100 mg/kg and indomethacin (5mg/kg) induced a significant reduction in pain response compared to the control group (p<0.05), while, pretreatment with NALOXANE and cyproheptadine inhibited some of the extract induced antinociceptive effects in comparison to control group (p<0.05).this study indicated that some of the antiniciceptive properties of z. tenuior are mediated by opioidergic and serotonergic mechanisms, which confirmed the traditional uses of the plant in the treatment of pain.

Objective: In the present study, the effect of bilateral intrahippocampal administration of histamine on anxiety-related behavior in rats was investigated. Method: The rats were first sensitized through 3 days of morphine administration and a 5 day drug-free period. The animals were then examined in a plus shaped maze. Results: Intra-VHC bilateral administration of histamine decreased %OAT (Open Arm Times) and %OAE(Open Arm Entries) but not locomotor activity, thus showing an anxiogenic response. However, the administration of histamine to morphine-sensitized rats increased OAT and OAE in comparison with saline administered groups, which is indicative of a decrease in anxiety in the sensitized animals. Conclusion: Bilateral administration of histamine in ventral hippocampus induces an anxiogenic effect, which decreases in morphine sensitized rats NALOXANE antagonizes the effects of morphine on anxiety.