Morphine-induced place preference: involvement of the central amygdala NMDA receptors

In the present study, the effects of bilateral injections of N-methyl-d-aspartate (NMDA) receptor agonist and/or antagonist into the central amygdala (CeA) on the acquisition and expression of morphine-induced conditioned place preference (CPP) were investigated in male Wistar rats. Animals that received 3 daily subcutaneous (s.c.) injections of morphine (1-9 mg/kg) or saline (1.0 ml/kg) indicated a significant preference for compartment paired with morphine in a dose dependent manner. Intra-CeA administration of the NMDA (0.01, 0.1 or 1 microg/rat) with an ineffective dose of morphine (1 mg/kg, s.c.) elicited a significant CPP. Administration of the non-competitive NMDA receptor antagonist, MK-801 (0.1, 0.3 or 0.5 microg/rat), into the central amygdala dose-dependently inhibited the morphine (6 mg/kg, s.c.)-induced place preference. Furthermore, intra-CeA administration of MK-801 (0.25, 0.5 or 1 microg/rat) reduced the response induced by NMDA (1 microg/rat, intra-CeA) plus morphine (1 mg/kg, s.c.). Neither NMDA nor MK-801 alone produce a significant place preference or place aversion. Moreover, intra-CeA injection of NMDA but not MK-801 before testing significantly increased the expression of morphine (6 mg/kg, s.c.)-induced place preference. NMDA or MK-801 injections into the CeA had no effects on locomotor activity on the testing sessions. These results suggest that the NMDA receptor mechanisms in the central amygdala may be involved in the acquisition and expression of morphine-induced place preference.     

Morphine-induced place preference: involvement of cholinergic receptors of the ventral tegmental area

In the present study, the effects of intra-ventral tegmental area injections of cholinergic agents on morphine-induced conditioned place preference were investigated by using an unbiased 3-day schedule of place conditioning design in rats. The conditioning treatments with subcutaneous injections of morphine (0.5-7.5 mg/kg) induced a significant dose-dependent conditioned place preference for the drug-associated place. Intra-ventral tegmental area injection of an anticholinesterase, physostigmine (2.5 and 5 microg/rat) or nicotinic acetylcholine receptor agonist, nicotine (0.5 and 1 microg/rat) with an ineffective dose of morphine (0.5 mg/kg) elicited a significant conditioned place preference. Furthermore, intra-ventral tegmental area administration of muscarinic acetylcholine receptor antagonist, atropine (1-4 microg/rat) or nicotinic acetylcholine receptor antagonist, mecamylamine (5 and 7.5 microg/rat) dose-dependently inhibited the morphine (5 mg/kg)-induced place preference. Atropine or mecamylamine reversed the effect of physostigmine or nicotine on morphine response respectively. The injection of physostigmine, but not atropine, nicotine or mecamylamine, into the ventral tegmental area alone produced a significant place aversion. Moreover, intra-ventral tegmental area administration of the higher doses of physostigmine or atropine, but not nicotine or mecamylamine decreased the locomotor activity. We conclude that muscarinic and nicotinic acetylcholine receptors in the ventral tegmental area may critically mediate the rewarding effects of morphine.     

Comparative effects of oral administration of Citrullus colocynthis and insulin injection on serum biochemical parameters of alloxan-induced diabetic dogs

Citrullus colocynthis seeds are traditionally used as antidiabetic medication in Mediterranean countries. An experiment was designed to evaluate the comparative effects of oral administration of C. colocynthis and insulin injection on the serum biochemical parameters of diabetic dogs. Twelve apparently healthy mixed breed dogs were selected and randomly allocated into three groups, two diabetic groups and one control group (n?=?4). Diabetes was induced with alloxan tetrahydrate. One diabetic group and the control group were treated with a dose of 100?mg/kg/day of C. colocynthis. Three days after confirmation of diabetes mellitus, the dogs were orally administered C. colocynthis capsules twice daily for 8?days. The other diabetic group was injected with a combination of neutral protamine Hagedorn (NPH) [insulin isophane (NPH)–Human-Exir] and regular crystalline insulin [insulin (regular)–Human-Exir] (70% NPH and 30% regular) twice daily for 8?days. Blood samples were collected from the cephalic vein at three time points: immediately before alloxan injection, 3?days after diabetic induction, and 12?h after the last treatment. Serum concentrations of glucose, insulin, triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, blood urea nitrogen, creatinine, alkaline phosphatase, alanine aminotransferase, and aspartic aminotransferase were measured. Results showed that the serum concentrations of glucose in insulin-injected dogs were not significantly different with those of the C. colocynthis-administered diabetic dogs. The serum concentrations of all measured parameters showed no significant change 8?days after the administration of C. colocynthis in the control group, whereas oral administration (capsule) of C. colocynthis at a dose of 100?mg/kg/day caused severe and mild diarrhoea in the control and C. colocynthis-treated diabetic groups, respectively. The present study indicated a significant antihyperglycaemic effect of C. colocynthis fruit and supports its traditional usage in the treatment of diabetes mellitus.     

Synthesis and biological evaluation of novel benzyl piperazine derivatives of 5-(5-nitroaryl)-1,3,4-thiadiazoles as Anti-Helicobacter pylori agents

Background and the purpose of the study

Helicobacter pylori is recognized as the main cause of gastritis and gastroduodenal ulcers and classified as class 1 carcinogen pathogen. Different 1,3,4-thiadiazole derivatives bearing 5-nitroaryl moiety have been shown considerable anti- H. pylori activity. In attempt to find new and potent derivatives of described scaffold, a new series of 1-(substituted benzyl)-4-(5-(5-nitroaryl-2-yl)-1,3,4-thiadiazol-2-yl)piperazine derivatives were synthesized and evaluated against three metronidazole-resistant isolates of H. pylori using paper disk diffusion bioassay test.

Methods

The title compounds were prepared through the reaction of 1-(5-(5-nitroaryl-2-yl)-1,3,4-thiadiazol-2-yl) piperazine 5a-b and substituted benzyl chloride in DMF. The inhibitory activity of the new derivatives 6a-q against three metronidazole-resistant isolates of H. pylori was evaluated by the disc diffusion method and compared with the commercially available standard drug metronidazole.

Results and discussion

The results of SAR study indicated that the potency and anti-H. pylori activity profile of synthesized derivatives is mainly attributed to the substituted nitroaryl moiety at the C-5 position of 1,3,4-thiadiazole ring. Most of 1,3,4-thiadiazole derivatives bearing 5-nitrofuran moiety at C-5 position of central thiadiazole ring, demonstrated more promising anti-H. pylori than the 5-nitrothiophen counterpart.

Conclusion

The most potent nitrofuran derivative containing 3-methoxybenzyl piperazine pendant at the C-2 position of 1,3,4-thiadiazole ring (compound 6i), demonstrated strong anti-H. pylori potential at studied concentrations 100-25 μg/disk (IZD > 20 mm) against all studied metronidazole- resistant isolates of H. pylori.     

Associations Between Coerced Anal Sex and Psychopathology,Marital Distress and Non-Sexual Violence

BackgroundThere is a dearth of scientific data on anal intercourse in heterosexual relationships. Likewise, anal sex within marital relationships has yet to be fully explored.ObjectivesAmong a representative sample of married women in the Iranian capital, Tehran, we aimed to determine the association of self-reported coerced anal sex with: (i) self-reported coerced vaginal sex; (ii) self-reported non-sexual violence; (iii) psychopathology; and (iv) marital attitude.MethodThe data presented here were obtained from the Family Violence Survey conducted in Tehran in 2007. A total of 230 married Iranian women were selected via a multi-cluster sampling method from four different randomized regions. The subjects' sociodemographic data, psychological distress (Symptom Check List; SCL-90-R), personality, and relationship characteristics (Personal and Relationships Profile), and marital attitude (Marital Attitude Survey) were gathered. In addition, the participants' self-reported histories of lifetime victimization through all types of violence by the husband, including coerced anal and vaginal sex as well as psychological and physical assault (Conflict Tactic Scales-Revised; CTS-2), were collected.ResultsThere were associations between self-reported victimization through coerced anal and vaginal sex (P < 0.001), psychological (P < 0.001), and physical aggression (P < 0.001). Those reporting to have been forced into anal intercourse cited higher rates of paranoid and psychotic features, jealousy, attribution of problems to one's own behavior, conflict, and male dominance, as well as lower expectations of improvement in one's marital relationship.ConclusionIn marital relationships, women are at a higher risk of coerced anal sex if subjected to other types of sexual or non-sexual violence. Higher rates of psychopathology and poorer marital relationships are also allied to self-reported anal sexual coercion. Mohammadkhani P, Khooshabi KS, Forouzan AS, Azadmehr H, Assari S, and Lankarani MM. Associations between coerced anal sex and psychopathology, marital distress and non-sexual violence. J Sex Med 2009;6:1938–1946.     

Blockade of NMDA Receptors and Nitric Oxide Synthesis Potentiated Morphine-Induced Anti-Allodynia via Attenuating Pain-Related Amygdala pCREB/CREB Signaling Pathway

The present study investigated the role of the amygdala N-methyl-d-aspartate (NMDA) receptors/nitric oxide synthase pathway in morphine-induced anti-allodynia. Concurrently with the bilateral cannulation of the central amygdala, chronic constriction of the sciatic nerve was performed on male Wistar rats. Morphine (3–5 mg/kg) was administered intraperitoneally to induce anti-allodynia. When D-AP5, a selective NMDA receptor antagonist, (.05–.1 µg/rat) or NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME), the nitric oxide synthase inhibitor (.1–.5 µg/rat), were microinjected into the central amygdala, the higher doses potentiated an ineffective dose of morphine (3 mg/kg). Microinjection of the same doses of D-AP5 and L-NAME without morphine had no effect. Comicroinjection of the ineffective doses of L-NAME (.1 µg/rat) and D-AP5 (.05 µg/rat) with a 5-minute interval, enhanced the anti-allodynic effect of morphine (3 mg/kg). Western blot analysis was employed to evaluate the levels of cyclic adenosine monophosphate-response element-binding protein (CREB) and phosphorylated CREB (pCREB) in the amygdala tissues. Our results showed that neuropathic pain increased the pCREB/CREB ratio in the amygdala, and this ratio was decreased after morphine-induced anti-allodynia. The potentiative effect of the coadministration of D-AP5/L-NAME on an ineffective dose of morphine also decreased the amygdala pCREB/CREB levels. Therefore, it seems that the amygdala pCREB/CREB signaling pathway plays a critical role in processing neuropathic pain. Moreover, the glutamate NMDA receptors and nitric oxide system in the amygdala may be involved in morphine-induced anti-allodynia.PerspectiveNeuropathic pain is difficult to treat and the exact mechanisms remain unknown. This article suggests the importance of the amygdala glutamatergic and nitric oxide systems in morphine-induced anti-allodynia. These findings might be used in clinical studies to reach a better understanding of neuropathic pain mechanisms and treatment.     

Methicillin‐resistant Staphylococcus aureus bacteraemia and epidural abscess in a neonate

A 24‐day‐old boy presented with fever, irritability and poor feeding. Blood culture grew methicillin‐resistant Staphylococcus aureus. Cerebrospinal fluid analysis showed pleocytosis, and methicillin‐resistant Staphylococcus aureus grew from enrichment broth. Magnetic resonance imaging revealed an epidural abscess extending from C2–3 to T8–9. Staphylococcal infections of the central nervous system are uncommon in neonates. This case demonstrates the importance of performing a lumbar puncture in isolated staphylococcal bacteraemia. The case also highlights that cerebrospinal fluid pleocytosis may indicate a parameningeal focus of infection.     

Comparing the analgesic effect of heat patch containing iron chip and ibuprofen for primary dysmenorrhea: a randomized controlled trial

ABSTRACT: BACKGROUND: Primary dysmenorrhea is a common and sometimes disabling condition. In recent years, some studies aimed to improve the treatment of dysmenorrhea, and therefore, introduced several therapeutic measures. This study was designed to compare the analgesic effect of iron chip containing heat wrap with ibuprofen for the treatment of primary dysmenorrhea. METHODS: In this randomized (IRCT201107187038N2) controlled trial, 147 students (18--30 years old) with the diagnosis of primary dysmenorrhea were enrolled considering the CONSORT guideline. Screening for primary dysmenorrhea was done by a two-question screening tool. The participants were randomly assigned into one of the intervention groups (heat Patch and ibuprofen). Data regarding the severity and emotional impact of the pain were recorded by a shortened version of McGill Pain Questionnaire (SF-MPQ). Student's t test was used for statistical analysis. RESULTS: The maximum and minimum pain severities were observed at 2 and 24 hours in both groups. The severity of sensual pain at 8, 12, and 24 hours was non-significantly less in the heat Patch group. There was also no significant difference between the groups regarding the emotional impact of pain at the first 2, 4, 8, 12 and 12 hours of menstruation. CONCLUSIONS: Heat patch containing Iron chip has comparable analgesic effects to ibuprofen and can possibly be used for primary dysmenorrhea.Trial registrationIRCT201107187038N2.     

Vaginal co-colonization with multiple Group B Streptococcus serotypes

Group B Streptococcus (GBS) is a neonatal pathogen frequently transmitted from maternal asymptomatic vagino-rectal colonization. Co-colonization with multiple GBS serotypes, which has implications for type-specific vaccination strategies, is difficult to detect with standard microbiologic techniques. We designed a nested real-time PCR assay to detect vaginal co-colonization in samples from a cohort of non-pregnant women (N?=?433). 6/91 (6.6%) GBS-positive samples harbored ≥2 GBS serotypes, with over-representation of serotype V among co-colonized samples. Serotype IV GBS was more prevalent (>10%) in this cohort than in previously reported United States studies. Ongoing surveillance of GBS serotype epidemiology and co-colonization is indicated.