Physiology and Pharmacology
Year:2003 | Volume:6 | Issue:2|Papers Count:14

Since long-term potentiation (LTP) is potentially the cellular basis of learning and memory, we studied the probable alterations of this phenomenon in hippocampal slices of morphine-dependent rats. Field EPSP (fEPSP) and orthodromic poulation spikes (OPS) were recorded from stratums radiatum and pyramidale of CA1 area following stimulation of Schaffer collaterals, in control and dependent slices respectively. To induce LTP, primed bursts (PBs) tetanic stimulation was used at frequencies of 100 and 200 Hz. The results showed that tetanus at a frequency of 100 Hz induced an enhanced OPS LTP in dependent slices as compared to control ones, while the magnitude of fEPSP LTP did not change in those slices. In response to 200 Hz tetanus, OPS LTP was induced in both control and dependent slices which was similar in magnitude, but different in time course. These findings suggest that OPS LTP can be proposed as a suitable electrophysiological tool for detection of long-term effects of chronic morphine exposure. In addition, morphine dependence may result in EPSP-Spike potentiation with a tendency toward VDCCs mechanisms in hippocampal CA1 synapses. Such probable changes in synaptic plasticity may underlie cellular and molecular bases of cognitive deficits as a result of opiate addiction.

Chronic constriction injury (CCI) is a commonly accepted model of neuropathic pain, which has been introduced by Bennett and Xie in 1988. This model contains the most usual characteristics of human neuropathic pain due to an increase in central sensitization like hyperalgesia and allodynia. It is a usual practice to apply acute pain stimulants such as thermal and mechanical ones for assessment of CCL In this experiment, formalin has been used as a chemical stimulant, which produces two phases of acute and chronic pain. In this way, the effect of CCI is not only determined in the acute phase, but also in the chronic phase, which the latter has a different mechanism of development. Furthermore, the role of formalin pain prior to CCI on formalin pain following CCI was also studied. Moreover, the role of intravenous injection of lidocaine, as a central pain blocker, before injection of formalin prior to CCI and its effect on the formalin pain post CCI was also investigated. The results showed that in the first phase of formalin test, CCI produced hyperalgesia at second day post CCI in the group which had sciatic ligation without formalin injection prior to CCI and hyperalgesia at day 14 post CCI in all groups, with or without formalin injection prior to CCI and the group who had lidocaine. In this respect, there were not any significant changes in the second phase of formalin test in all groups, except for hyperalgesia at second day post CCI in the group which had not received formalin prior to CCI.

Local anesthetic agents are well known to interrupt impulse conduction in peripheral nerve axons when applied locally in high concentration. The phenylpiperidine opioid, meperidirie, in addition to its systemic opioid effects, also shows local anesthetic-like action, when applied directly to peripheral nerves. The opioid meperidine induces anesthesia and blocks action potentials. The local anesthetic effects of meperidine has been demonstrated in both clinical and laboratory studies. Clinically, it can produce segmental sensory anesthesia. However, most of the previous studies on the effects of meperidine on nerve conduction have all made use of peripheral nerve preparations and yielded conflicting results. In the present study, we have characterized the effects of meperidine on ionic currents underlying neuronal excitability, using current-clamp and two-electrode voltage-clamp techniques. The results showed that FI neurons of the garden snail, Helix aspersa, respond to meperidine by significantly decreasing the peak amplitude and significantly increasing the duration of action 11 potentials. Voltage-clamp experiments revealed that meperidine depressed the macroscopic inward and increased outward K + currents. In conclusion, these findings indicate that meperidine decreases the excitability in Helix aspersa nervous system by decreasing inward ionic currents and increasing outward currents underlying the action potential.

Time-dependent reversal of primed burst-induced long-term potentiation (LTP) was investigated in the CA1 region of rat hippocampus following theta pulse stimulation (TPS) of Schaffer collaterals. The effect of TPS (5Hz, 900 pulses) on primed burst potentiatin was evaluated through the analysis of the slope of population excitatory post-synaptic potentials (pEPSPs) and amplitude of population spikes (PSs). TPS had no lasting effect on baseline synaptic responses, while produced a lasting depression of previously potentiated responses when delivered 3 mm after LTP induction. TPS produced progressively lower depotentiation at longer delays, until it had no effect 20 min after LTP induction. These results suggest that the hippocarnpal theta rhythm promotes the induction of LTP as well as its subsequent reversal. Reversal of LTP may function to refine memories and prevent saturation of the storage capacity of the neural network.

In the present study the correlation between the development of hypertension and local (including aorta, heart, kidney, lung) as well as circulatory (serum) ACE activity in two kidney, one clip (2 Kl C) renovascular model of hypertension was investigated.For this purpose, left renal artery clipping were performed on 10- to 12-weeks old rats. Experiments were carried out in 2, 4, 8, and 12 weeks after surgery (2W, 4W, 8W and 12W). After sacrificing, animal's blood sample and tissues including heart, aorta, lung and kidney were dissected out and homogenized in Trizma buffer. ACE activity was determined by hydrolysis of the synthetic substrate, Hip-His-Leu and the amount of hippuric acid released from the substrate were analyzed by HPLC. The results showed that the systolic blood pressure (SBP) was gradually increased in 2 Kl C animals and was markedly higher as compared to that of controls. The ACE activity in all tissues from 2 Kl C was significantly different in all groups. The serum ACE activity of 2 KIC animals was markedly increased in 2W and 4W and reached to a plateau in 8W and 12W groups. These results indicated that there is a positive correlation between augmentation of blood pressure and local ACE activity in various tissues as well as serum, highlighting the significant contribution of local ACE activity as compared to its circulatory one in the development of renovascular hypertension.

Extensive evidence strongly suggest that modest increases in circulating glucose modulate learning and memory processes, but researches on elucidating the physiological basis of this action are still continuing. In the present study, we investigated the effect of glucose on amnesia induced by the non-competitive NMDA antagonist, Mk-80l in rats. AY-maze apparatus, controlled by computer, was used for active avoidance conditioning in male NMRI rats. The first group of rats received 1000 mg/kg of glucose immediately following the training, the second groups received 0.06 mg/kg of Mk-80 I 30 min before training and the third group received Mk-801 (0.06 mg/kg) before training and glucose (1000 mg/kg) after training, while control groups received only saline at the same volume. The results showed that glucose not only does improve the dementia induced by Mk-BOI (P<0.01), but also it increases the learning process (P<0.05). It can be concluded that glucose might have played its most effects through mechanisms other than NMDA receptors.

Atrial natriuretic peptide (ANP) is a 28 amino acid hormone secreted by atrial myocytes in response to local wall stretch. The effects of this hormone on target tissues (kidney, adrenal gland and smooth muscle) include the regulation of sodium, potassium, blood volume and blood pressure. In the present study, ANP extracted from sheep atria was used and its physiological effects were investigated. For this purpose, 40 g of sheep atrial tissue was homogenized at 40 °C in a buffered solution containing protease inhibitor substance. Homogenized tissue was centrifuged at 2500g for 10 minutes and the supernatant boiled for 10 minutes, then centrifuged again in 10000g. The results -indicated that after i.p. injection of sheep atrial extract to the experimental animals, the level of hematocrit increased (P<0.005) (This is probably through renal excretion of salt and water). Furthermore, injection of sheep atrial extract produced a decrease in blood pressure (P<0.05). In this respect, the maximum effect was observed after 25 minutes. The fall in blood pressure was also as a result of ANP direct effects on smooth muscles of the blood vessels as well as inhibition of the renin-angiotensin system. Following 25 and 35 minutes, hypertension developed (This is as a result of the interactions among blood pressure control systems). This was followed by another decreases in blood pressure after 45 minutes, probably due to increased renal tubular excretion of salt and water).

In the present study, the effects of excitation and inhibition of GABAA and GABAB receptor subtypes on the expression of morphine-induced conditioned place preference (CPP) were investigated. For this purpose, male Wistar rats (250-300 g) were used in the experiments. Five days after surgical cannulation in the ventral tegmental area (VTA), different doses of morphine were injected into the animals and conditioned biased method was applied. The results showed that subcutaneous injections of morphine sulfate (1-10 mg/kg) induced CPP in a dose-dependent manner. Furthermore, administration of GABAA receptor agonist, muscimol (6 ng/rat) into ventral tegmental area reduced the morphine effects. The drug at doses of 12 and 25 ng/rat enhanced morphine-induced CPP. Reduction of morphine-induced CPP was observed following injection of GABAA receptor antagonist, bicuculine (6, 12 and 25 ng/rat) into VTA. Injection of baclofen as GABAB receptor agonist (6 ng/rat) into VTA caused an increase in CPP induced by morphine, whereas the drug at doses of 12 and 25 ng/rat reduced the morphine effects. Injection of CGP38345 (a GABAB receptor antagonist) into the VTA at doses of 6, 12 and 25 ng/rat significantly reduced the CPP induced by morphine. It could be concluded that excitation and inhibition of GABAA and GABAB receptor subtypes in the VTA may have different effects on morphine-induced CPP.

It has been reported that nicotine induces many of its effects via increasing the production of nitric oxide (NO). In the present study, the possible role of NO in the induction of rewarding effects of nicotine was investigated, using conditioned place preference (CPP) in male Swiss-Webster mice (20-25 g). The results showed that injection of nicotine (0.25-2 mg/Kg, i.p.) and L-arginine (NO precursor) (50-500 mg/Kg, i.p.), but not mecamylamine (0.05 and 0.1 mg/Kg, i.p.) and L-NAME (nitric oxide synthase inhibitor) (5-20 mg/Kg, i.p.) to the animals produced a significant but not dose-dependent CPP. Administration of mecamylamine (0.05 and 0.1 mg/Kg, i.p.) or L-NAME (5-20 mg/kg, i.p.) before nicotine (1. mg/Kg, i.p.) or L arginine (200 mg/Kg, i.p.) significantly abolished the CPP induced by above-mentioned drugs. When the antagonists were administered 15 min before the test to those animals which received nicotine (1 mg/Kg, i.p.) or L-arginine (200 mg/Kg, i.p.) in the training days, the effects of the agonists did not change. Administration of ineffective doses of L-arginine (50, 100 and 150 mg/Kg, i.p.) in combination with ineffective dose of nicotine (0.6 mg/Kg, i.p.) potentiated the epp induced by nicotine. However, injection of L-arginine at these doses in the test day to those animals which received nicotine (1 mg/Kg) in training days reduced the response to the nicotine. The same results were obtained when ineffective doses of nicotine (0.25, 0.5 and 0.75 mg/Kg, i.p.) were administered with ineffective dose of L-arginine (50 mg/Kg, i.p.). Furthermore, nicotine (0.25, 0.5 and 0.75 mg/Kg) when administered before the test to those animals which received L-arginine (200 mg/Kg) in the training days reduced the expression of epp induced by L-arginine. In conclusion, it can be suggested that NO may play an important role in nicotine rewarding effects as investigated by CPP paradigm.

Recent evidences have shown that morphine has peripheral analgesic effects. In this study, the effect of local and chronic administration of morphine on lidocaine-induced local sensory block was investigated using a rat model of peripheral analgesia. The experiments were performed on adult male Sprague-Dawley rats (180-250 g; n=6) in 5 groups: 1) saline + saline (control), 2) morphine + saline, 3) lidocaine-saline, 4) morphine + lidocaine, 5) lidocaine+ saline in addicted rats (animals received cmomc doses of morphine in their drinking water for 21 days). In all groups, pain tolerance was assessed using hot plate test (55±0.5°c) on paw licking behavior before and 16 min after drug administration. The anti-nociceptive effect of intraplantar morphine (200, 400, and 800 µg), lidocaine (0.25, 0.5, 1, and 2%), Co administration of non-analgesic doses of morphine (200 µg) and lidocaine (1 %) in non-addicted rats and lidocaine (0.25, 0.5, 1, and 2%) in addicted rats were evaluated. The results showed that intraplantar injection of lidocaine produced analgesic effect in both addicted and non-addicted rats compared to controls. Furthermore, morphine produced local anti-nociceptive effect. Co administration of non-analgesic doses of morphine and lidocaine produced a potentiated analgesic effect. Meanwhile, the analgesic effect of lidocaine was potentiated in addicted rats. These data support that local and chronic use of morphine can potentiate local analgesic effect of lidocaine.

Propranolol and yohimbine are two antagonists of adrenergic receptors (Beta and Alfa2 respectively), blocking the actions of catecholamines. Besides a number of effects on metabolic processes, catecholamines influence the body immune system (i.e. the activity of macro phages). As in other vertebrates, macrophages of the fish play a critical role in getting rid of the pathogenic particles. However, the depressive effect of increased levels of catecholamines on phagocytic activity of macrophages has not been investigated yet. Therefore, for studying this effect on phagocytic activity, suspensions from pronephros of rainbow trout were prepared. Increasing doses of propranolol or yohimbine (0, 0.5, 1, 2.5, 5 and 10 mg/ml) were added to the suspensions. The suspensions were then incubated with adrenaline (4 µg/ml). The results indicated that a significant decrease (P<0.01) in phagocytosis existed in suspensions incubated with adrenaline alone. Furthermore, a significant increase (P<0.01) in phagocytosis was observed in suspensions incubated with either of the antagonists plus adrenaline. In addition, the effect of yohimbine was greater than the effect of propranolol (P<0.01). These results suggest that both propranolol and yohimbine could inhibit the depressant effect of adrenaline on the phagocytic activity of macrophages in rainbow trout.