32 24765236 Iranian Society of Physiology and Pharmacology 309 Role of NMDA receptors and voltage-dependent calcium channels in augmenting long-term potentiation of the CA1 area in morphine-dependent rats Motamedi Fereshteh Pourmotabbed Ali Fathollahi Yaghub Mansouri Farshad Alizadeh Semnanian Saeed 1 11 1997 1 2 84 96 01 08 2007 15 05 2014   The involvement of NMDA receptors and voltage-dependent calcium channels in augmentation of long-term potentiation (LTP) was investigated at the Schaffer collateral CA1 pyramidal cell synapses in hippocampal slices of morphine dependent rats, using primed-burst tetanic simulation. The amplitude of the population spike and its delay were measured as indices of increase in postsynaptic excitability. D,L-APV and nifedipine were used as an NMDA receptor antagonist and a voltage-dependent calcium channel blocker, respectively. The amount of LTP of the orthodromic population spike (OPS) was higher in slices from dependent rats. Perfusion of slices from control and dependent rats with ACSF containing D,L-APV (25 µ M) and delivering tetanic simulation showed that D,L- APV completely blocked the LTP of OPS in slices from both control and dependent rats, while nifedipine (10 µ M) attenuated the amount of LTP of OPS in dependent slices and had no effect on controls. The results suggest that the enhanced LTP of OPS in the CA1 area of hippocampal slices from morphine-dependent rats is primarily induced by NMDA receptor activity, and the voltage-dependent calcium channels may also be partially involved in this phenomenon.
310 Effect of imipramine and desipramine on adenosine receptors in isolated rat atria 1 11 1997 1 2 97 104 01 08 2007 15 05 2014   The effect of different doses (1-50 µ M) of imipramine (IMI) and desipramine (DES) on the rate and force of contraction of isolated rat atria was studied. IMI and DES produced a dose-dependent increase in force of contraction (31- 94% for IMI and 35-118% for DES). Pretreatment of rats with reserpine (5 mg/kg) on the isolated atria with propranolol (1 µ g) inhibited the positive ionotropic effect of both drugs. The two antidepressants IMI and DES showed a dose-dependent decrease in rate of contractions (19-87% and 16-88%, respectively). The positive ionotropic and negative chronotropic effects induced by these drugs was significantly prevented by a selective A1 antagonist (DPCPX, 3 µ M). The effects of IMI (5 µ M) and DES (5 µ M) the rate and contractile force was inhibited by atropine (10 nM). The selective A2 antagonist (DMPX, 1.5 µ M) prevented the ionotropic effect produced by IMI and DES. We conclude that in rat atria, the positive ionotropic action of IMI and DES is due to their action on adrenergic, muscarinic, adenosine A1 and A2 receptors, and Ca2+ influx or release from intracellular storages of the rat myocytes. The negative chronotropic action of these two drugs is probably due to the involvement of adenosine A1 receptors and cholinergic mechanisms. 311 Role of the adrenergic system in physostigmine-induced yawning 1 11 1997 1 2 105 110 01 08 2007 15 05 2014 In this study the effect of adrenergic receptor agonists and antagonists on physostigmine induced yawning was investigated. Intraperitoneal injection of different doses of physostigmine (0.03, 0.05, 0.1 and 0.2 mg/kg) caused yawning in white rats. The greatest response was seen at a dose of 0.2 mg/kg physostigmine. Phenylephrine, an α1 agonist, and clonidine, an α2 agonist, led to a decrease in physostigmine-induced yawning. Prazosine and high-dose phenoxybenzamine decreased the inhibitory effect of phenylephrine. Also, high doses of yohimbine decreased the effect of clonidine. Adrenergic receptor antagonists phenoxybenzamine, prazosine and propranolol had no significant effect on the physostigmine-induced response, while the α2 antagonist (yohimbine) and low-dose prazosine decreased physostigmine's effect. Based on these results, we may conclude that activation of α1 and α2 receptors leads to a decrease in physostigmine-induced yawning in rats. 312 Extent of branching and conduction velocities of ascending and descending primary afferents in isolated spinal cord of the rat and hamster 1 11 1997 1 2 111 115 01 08 2007 15 05 2014 Wall and Shortland (1991) have shown that afferent fibers entering the cord in thoracic and lumbar roots of adult rats have branches that may penetrate up to 11 segments caudally from the root entry zone. We have investigated the extent of branching and conduction velocities of ascending and descending branches of lumbar and thoracic primary afferents in isolated spinal cords of adult hamsters (60-110 g) and juvenile rats (30-46 g). Hemisected spinal cords were maintained at cold artificial cerebrospinal fluid (25-27 °C) in which the Ca2+ had been replaced by Mn2+ (2 µM) to block synaptic activity. Hamsters' antidromic conducted responses were obtained up to 10 segments caudal to dorsal roots T6- T7 and 17 segments rostral to L3. The mean conduction velocity was 3.7 m/s (S.E.M. ± 0.4) for descending primary afferents (n=2l) and 9.9 ± 1.2 m/s for ascending afferents (n=26). In the rat, antidromic responses were measured over 4 segments caudal and 17 segments rostral to the L3 dorsal root. Conduction velocities were 4.4 ± 0.5 m/s and 7.7 ± 0.7 m/s for descending and ascending branches, respectively (n=4). The results were similar to those reported by Wall and Shortland, although the temperature difference between the in vitro and in vivo preparations would have resulted in approximately halving of the velocity in isolated cord preparation. The conduction velocity of descending fibers was about half of ascending fibers which may be related to the differences within the branches. 313 Role of dopaminergic receptors in acute joint inflammation in the rabbits 1 11 1997 1 2 116 122 01 08 2007 15 05 2014   The dopaminergic system has different effects on the cardiovascular and immune systems. Since both vascular injuries and activation of the immune system are involved in joint inflammation, in the present study the role of dopaminergic receptors in knee joint inflammation was studied. Evans blue (75 µ g/kg) was used in order to observe changes in permeability which occurred during the process of inflammation. Inflammation was induced by injection of 1 ml kaolin (4 %) into the knee joint of the rabbit. This process was studied on different hours (2, 4, 8 and 24). Maximum inflammation was achieved after 4 hours. SKF38393, a Dl agonist, reduced knee joint inflammation. This response was dose-dependent. Also, injection of SCH23390, a Dl antagonist, prior to SKF38393 injection, attenuated its effects dose-dependently. Using SCH23390 per se did not affect the kaolin-induced inflammation. In another group, nifedipine, a calcium channel blocker, reduced the anti-inflammatory effect of SKF38393. The effects of LY171555, a D2 agonist, and sulpiride, a D2 antagonist, were also studied, and no significant changes were observed. 314 Suppression of acute and chronic pain in male rats by alcoholic extract of Sambucus ebulus Ahmadiani Abolhassan Semnanian Saeed Fereydouni Masoud 1 11 1997 1 2 123 128 01 08 2007 15 05 2014   Pharmacologists believe analgesic and anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioid compounds, due to their side-effects and, in some cases, inadequacy, are not always useful. Therefore it seems necessary to search for newer analgesic compounds. In traditional Iranian Medicine, the leaf and rhizome of Sambucus ebulus is used as a topical medication in the treatment of pain caused by bee stings, nettle stings and joint inflammation. We therefore decided to study the analgesic effects of this plant. Two methods, the tail flick test for acute pain and the formalin test for chronic pain were employed to measure pain. Analgesic effects of 50, 100 and 200 mg/kg doses of S. ebulus rhizome extract were compared with 300 mg/kg sodium salicylate as a positive control. The plant extract relieved pain in the tail flick test and in both phases of the formalin test, while sodium salicylate only treated pain in the formalin test. In none of the two tests was naloxone effective in inhibiting the analgesic effect of S. ebulus extract. Phytochemical investigations and previous reports suggest flavinoids to be the probable analgesic compounds. 315 Effect of cisplatin treatment on the response to serotonin 1 11 1997 1 2 129 132 01 08 2007 15 05 2014   Although cisplatin is one of the most effective cancer drugs which is widely used in the treatment of various neoplasms, its side effects, especially vomiting may limit its use. It has been demonstrated that cytotoxic drugs lead to a sudden release of serotonin (5-HT). The following study was performed to determine the possible interactions of cisplatin with 5-HT receptors. In this study, the effect of pretreatment with cisplatin on the contractile response of guinea pig ileum to serotonin was investigated. The contractile response of ileal tissue to various agonists was recorded using a Bio-Science isotonic transducer and a model 400 MDR Washington oscilloscope. All drugs were diluted in distilled water and Tyrode's solution to achieve the desired concentration before being added to the organ bath. Statistical significance was evaluated using the t-test. It was found that serotonin produces a biphasic contractile response in the isolated guinea pig ileum. Addition of cisplatin (10-7 M) in the organ bath did not affect the contractile response to 5-HT. Pretreatment of guinea pigs with cisplatin (10 mg/kg/day, i.p.) for two days only resulted in a reduction of the contractile response to low concentrations of 5-HT. Pretreatment with cisplatin did not affect the contractile response to acetylcholine. We conclude that cisplatin pretreatment results in the selective destruction of some 5-HT receptors other than the 5-HT3 receptor. 316 Effects of two new dihydropyridine derivatives, mepudipine and dibudipine, on isolated human internal mammary artery and rat left atrium 1 11 1997 1 2 133 138 01 08 2007 15 05 2014   Among the present classes of calcium channel blockers, dihydropyridine derivatives are widely used in the therapy of hypertension, angina pectoris and the other cardiovascular diseases. Since the prototype of dihydropyridine derivatives, nifedipine, does not have the optimum pharmacokinetic and pharmacodynamic characteristics, several attempts have been made to synthesize other drugs in this class with improved properties. In the present study, the effect of two new dihydropyridine derivatives, mepudipine and dibudipine, on isolated human internal mammary and rat left atrium is investigated. The two newly synthesized compounds could relax K+-treated internal mammary arteries. Their potencies to elicit this effect were comparable with that of nifedipine. The potency of these compounds for reducing the contraction force of rat left atrium was significantly lower than that of nifedipine. These compounds did not show any significant difference with each other in this respect. As reported in our previous study, mepudipine and dibudipine showed potent vasodilatory effects. Since they have weak action on the rat atrium, we conclude that the two new compounds are more vasoselective than nifedipine. Also, their effect on the internal mammary artery confirms their vasodilatory action in the human artery.