Physiology and Pharmacology
Volume:3 Issue: 1, 1999

It has been revealed that dopamine (DA) modulates gastro-duodenal responses to stress. Several investigations have been made to identify the mechanisms and/or receptors by which DA or its promoters exert their gastroprotective function against stress, however there are many discrepancies in this respect. In order to clarify the relative contribution and/or interaction of two DA receptor subtypes (Dl and D2) on stress-induced gastric ulcer (SIGU), their selective agonists including SKF-38393 (SKF) and quinpirole (QPL) were used. For this purpose the agonists were injected (i.p. alone and/or in combination) to individual groups of rats. Some doses of SKF and QPL were injected i.p. (5 mg/kg) and i.c.v. (1 µg/rat), 60 and 30 min before stress induction respectively. Gastric ulcer was developed invariably by using a model of restraint and cold immersion stress. Both SKF and QPL reduced significantly the index and severity of SIGU. SKF was more effective after i.p. administration, however the effect of QPL was greater when it was injected i.c.v. When both SKF and QPL were injected i.c.v., their protective effects on SIGU were enhanced significantly. When SKF was injected i.p. and QPL injected i.c.v., the ulcer index and severity diminished more significantly, indicating a potentiation of their effects on SIGU. It is concluded that both central and peripheral DA receptors (Dl and D2) modulate gastric function and protective response to stress, however peripheral Dl and central D2 receptors are more involved in gastroprotective effects of DA-agonists and the protection is maximal when these two receptors are stimulated concurrently.

The effects of goitrogens on the thyroid gland have been much studied and calcium is considered as a goitrogen in some cases. Since the level of calcium is high in drinking water of some cities of Khozestan province, the effects of high calcium intake on the function of thyroid gland is investigated in this study. For this purpose the concentration of thyroid hormones is measured in rats. The study was carried out on 73 male and female rats. The animals were divided into 3 groups, control group with nonnal diet (n=25), group 2 (n=24) consumed diet with high calcium (1 g/kg diet) and group 3 (n=24), had diet with high calcium and iodine (50 µg/kg diet). Animals had free access to diet and water. The rats were decapitated after 1.5 and 3 months, blood samples were collected, centrifuged and the sera were stored at -20°C. Hormones (T3, T4 and TSH) and T3 uptake were measured by radioimmunoassay method, using commercially available kits (Kodak, England). The results indicated that the amount of T3 in the test group was not significantly different from that of control group. The results showed that in the groups which consumed diet containing high calcium and iodide, mean total T4 concentration was significantly higher than control (p<0.05). Measurement of T3 uptake showed that in the test groups, T3 uptake was significantly lower than control. This may be due to increased synthesis of proteins, less hormone synthesis, or abnormality of the protein binding to the hormones. In general the results are predictable with the known concepts.

The effectiveness of θ pattern primed-bursts (PBs) on development of primed-burst (PB) potentiation was investigated in layer II/III of the adult rat visual cortex in vitro. Experiments were carried out in the visual cortical slices. Population excitatory post-synaptic potentials (pEPSPs) were evoked in layer II/III by stimulation of either white mater or layer IV. To induce long-term potentiation (LTP), eight episodes of PBs were delivered at 0.1 Hz. Regardless of stimulation site, field potential recorded in layer II/III consisted of two components: a short latency and high amplitude response called pEPSP1, and a long latency and low amplitude response called pEPSP2. The incidence of LTP produced by PBs of layer IV was higher than that of the white mater tetanization. In contrast, PBs of both layer IV and white mater reliably induced LTP of pEPSP2 in layer II/III. It is concluded that PBs, as a type of activity pattern, of either white mater or layer IV can gain access to the modifiable synapses that are related to pEPSP2 in layer II/III, but accessibility of the modifiable synapses that are related to pEPSP1 depends on tetanization site. Relevancy of the results to the plasticity gate hypothesis is also discussed

There is evidence indicating that adrenoceptor mechanisms may influence some of the behaviors in rat. However the role of adrenoceptor agents on sniffing has not been identified. In the present study, the influence of adrenoceptor agents on sniffing induced by apomorphine and amphetamine has been investigated. Male Albino rats, weighing 150-250 g were used for all experiments. The behavior was measured based on the method we used previously. Sniffing was scored every 15 sec according to the following scale: 0=absent, 1=sniffing. At each 60 min period, the sniffing score ± SEM of at least 9 rats was scored; Score 0 indicates no sniffing, score 240 indicated maximum sniffing. Effects of adrenergic agonists and antagonists on sniffing induced by amphetamine and apomorphine have been tested in rats. Intraperitoneal (IP) administration of different doses of amphetamine (2-8 mg/kg) induced a dose-related sniffing. IP administration of apomorphine (0.5 mg/kg) also induced sniffing. Different doses of clonidine, phenylephrine and prazocin decreased sniffing induced by both amphetamine and apomorphine. Yohimbine reduced inhibitory influence of clonidine on amphetamine- and apomorphine-induced sniffing. However the response of phenylephrine was not altered by prazocin pretreatment. It is concluded that α2 adrenoceptor stimulation is able to reduce sniffing induced by dopaminergic system.

The effects of gentamicin, lithium and combination of these drugs on ultrastructural morphology of rat submandibular glands were studied. Daily intraperitoneal injection of 40 mg/kg of gentamicin which causes chronic salivary gland toxicity, led to a marked decrease in gland''s dry weight and total protein concentration but did not affect DNA content. Electron micrograph (EM) of submandibular acinar cells showed electron dense, whorls of rough endoplasmic reticulum and swollen mitochondria. Chronic treatment by lithium also caused a significant decrease in gland''s dry weight and total protein concentration. Contrary to gentamicin, lithium treatment caused a significant increase in gland''s DNA content but did not cause hyperplasia or hypertrophy of the cells as indicated in EM. Lithium also caused swelling of rough endoplasmic reticulum of acinar cells, Concurrent treatment by lithium and gentamicin increased the total protein concentration up to those of control values. Combination therapy significantly decreased gland''s dry weight when compared with those of gentamicin and lithium alone. EM also showed extended cellular changes including swollen, electron dense and whorls of rough endoplasmic reticulum. Lithium concentration was considerably increased in submandibular gland as a result of combination therapy. We also observed unexplainable alterations in rat submandibular gland induced by lithium and gentamicin alone or combination therapy that some of them could be due to interactions of these drugs with intracellular cAMP or phosphoinositides second messenger pathways.

Clonidine, an α2-adrenergic receptor agonist not only induces analgesia but also prolongs the effects of local anesthetic substances. In the present study the effects of clonidine on spontaneous and formalin-induced electrical activity from dorsal skin nerve were investigated. The results showed that clonidine (0.5 mM) decreased the formalin effect on electrical nerve activity whereas clonidine (5 mM) increased it. Co-administration of clonidine (0.5 mM) and lidocaine (0.5 mM) in the presence of formalin decreased the electrical nerve activity. Co-administration of clonidine (5 mM) and lidocaine (0.5 mM + formalin 0.2%) increased nerve activity. In conclusion, clonidine at low concentration (0.5 mM) exhibited mild anesthetic effect and also potentiated the anesthetic effect of lidocaine whereas in high dose (5 mM) showed opposite effect.

Clonidine, an α2-adrenergic receptor agonist not only induces analgesia but also prolongs the effects of local anesthetic substances. In the present study the effects of clonidine on spontaneous and formalin-induced electrical activity from dorsal skin nerve were investigated. The results showed that clonidine (0.5 mM) decreased the formalin effect on electrical nerve activity whereas clonidine (5 mM) increased it. Co-administration of clonidine (0.5 mM) and lidocaine (0.5 mM) in the presence of formalin decreased the electrical nerve activity. Co-administration of clonidine (5 mM) and lidocaine (0.5 mM + formalin 0.2%) increased nerve activity. In conclusion, clonidine at low concentration (0.5 mM) exhibited mild anesthetic effect and also potentiated the anesthetic effect of lidocaine whereas in high dose (5 mM) showed opposite effect.

Various recent studies in both human and laboratory animals have indicated an influential role of glucose and phosphate in embryonic development of different strains and species in various media. So this study was initiated to investigate the effects of different concentrations of glucose (G0=0, Gl=0.2, G2=5.5 mM) in the absence (P0) and presence (P1=0.39 mM) of inorganic phosphate, designated G0P0, G0Pl, G1P0, G1Pl, G2P0, G2P1 in M16, CZB and T6. EDTA (0.02 mM) and BSA (4 mg/ml) were added to all media. Mouse embryos (NMRI strain) were cultured from one-cell stage (24-26 h post hCG) for 120 h. Every 24 h, all embryos were scored in each treatment for the stage of development attained during 5 days, and embryos in treatments of T6 were stained to determine final cell number. After 120 h, comparison of hatching blastocyst rate in treatments of T6 did not exhibit differences (56-69%) but the blastocysts from G1P1, G0P0 and G2Pl had significantly more blastomere than G0P0, G0Pl and G1P0 (90 ± 95, 106 ± 5, 103 ± 4, 140 ± 6, 128 ± 5 and 134 ± 5 respectively). Also after 96 h and 120 h, embryos from the treatments of M16 and CZB that included glucose, had a significantly higher hatching blastocyst compared to embryos developed in free-glucose treatments (after 96 h in M 16, 8-15% vs 0% and after 120 h in CZB 52% vs 1625%). Best results in terms of sustaining development to hatching blastocyst were obtained with T6>CZB>M16. These results show that not only the glucose and phosphate have no inhibiting effect on the development of one-cell NMRl mouse embryos to the hatching blastocyst stage in M16, CZB and T6, but also in the presence of glucose the development and cleavage rates increase.

Effects of visual deprivation on the induction of epileptiform activity were studied in layer II/III of mature rat primary visual cortex. Field potentials were evoked by stimulation of layer IV in slices from control and dark-reared (OR) rats. Picrotoxin (PTX)-induced epileptic activity was characterized by spontaneous and evoked epileptic field potentials (EFPs). The results showed that OR slices demonstrate greater susceptibility for induction of spontaneous EFP. PTX-induced changes in the properties of evoked field potentials also showed higher tendency of OR animals to epileptogenesis. In both groups, field potentials are consisted of pEPSP1 (population excitatory post-synaptic potential 1, i.e. first negativity) and pEPSP2 (second negativity). PTX significantly increased the amplitude and duration of pEPSP2, but it had no significant effect on pEPSP1. PTX-induced changes in characteristics of pEPSP2 were significantly higher in OR slices. It is concluded that visual deprivation causes lasting changes in layer II/III of visual cortex that retain in slices and predispose this area for PTX-induced epileptiform activity.

In this study interaction of three types of calcium channel blockers; nifedipine, diltiazem and verapamil on the effects of lead acetate on two types of pain (nociception and inflammation) induced by formalin in mice were examined. In order to study nociception, formalin test was selected because of greater resemblance to clinical pain. Lead acetate (50, 75, l00, 125 and 150 mg/kg) administered intraperitoneally 90 minutes before formalin injection. Nifedipine (5 mg/kg), diltiazem (10 mg/kg) and verapamil (5 mg/kg) alone or in combination with different doses of lead acetate were used. Different doses of lead acetate induced a dose-dependent anti- nociception in both phases of formalin test. When animals were administered alone by calcium channel blockers, among them diltiazem and verapamil did not induce any significant effect in both phases of formalin test but nifedipine induced anti-inflammatory effect in late phase significantly (p<0.01). Pretreatment of animals with nifedipine and verapamil potentiated lead acetate anti-nociceptive effect (early phase) in doses of 50, 75 and 50 mg/kg, respectively. Both nifedipine and diltiazem augmented lead acetate anti-inflammatory effects (late phase) in all doses used. Pretreatment of animals with verapamil did not affect lead acetate anti-nociceptive or anti-inflammatory effects. Based on these data, tile association between calcium channel blockers and lead may be explained as a synergistic action rather than a simple dose combination of both agents. It is concluded that L-type calcium channels are susceptible to lead acetate that may be blocked during lead poisoning but different L-type calcium channel subtypes have different sensitivity to lead neurotoxicity.

Bibliographical studies have been done on plants that are used as analgesics in traditional medicine, and Mellissa officinalis or Lemon Balm (LB) that there are some evidence indicating for its application as analgesics or its probable analgesic effect was selected for evaluation of analgesic effect by tail-flick test in mice. After scientific identification, the leaves and flowered branches of LB were used for extraction by two methods, perculation and suxhelet. Male Albino mice, weighing 20-30 grams and aging 4-6 weeks, were utilized in 9-inserted groups. Methanolic perculated extract of LB with different doses 50, 75, 100, 200 and 300 mg/kg were injected intraperitoneally to experimental animals. Suxhelet extract was injected with a dose of 200 mg/kg. Aspirin 300 mg/kg and morphine 2.5 mg/kg were injected into the positive control groups and normal saline 10 ml/kg was injected into the negative control groups. The analgesic effect of the plant extracts and the drugs was measured for 120 in periods of 15, 30, 45, 60, 90 and 120 minutes after injection. The results show that LB extract has analgesic effect and the most analgesic effect was induced by 200 mg/kg of extract 15 minutes after injection. However, perculation extract has more analgesic effect than suxhelet extract. There are no significant differences between the analgesic effect of LB extract with morphine 2.5 mg/kg in the 15, 90 and 120 min and ASA 300 mg/kg in the 15, 60 and 90 min after injection.

Population explosion is one of the problems of developing countries today. This topic has been evaluated from different standpoints. From a family point of view a variety of contraceptive devices and medications have been devised and used. At present, the available mean in men is only vasectomy (surgical and non-surgical) barrier method (condom). Since the available methods and medications do not meet all requirements and needs of the couples, development of new and effective anti-fertility agents can successfully obviate the deficiency of the common and available method and medications. In this research we have evaluated the effects of nitrofurantoin on the process of male rats spennatogenesis, fertility and steroidogenesis. The agent has been administered subcutaneously 30 mg/kg twice a day for 50 days. Changes in the values of the indices indicate that the drug exerts an inhibitory effect with significant results on the process of spermatogenesis and fertility and does not show any effect in the process of steroidogenesis.