Physiology and Pharmacology
Volume:4 Issue: 2, 2000

The effect of cysteamine, a somatostatin depletor, on synaptic plasticity induced by tetanic and paired-pulse stimulation was investigated in rat hippocampal CA1. For this purpose, hippocampal slices from saline (1 ml/kg, s.c.) and cysteamine (200 fig/kg, s.c.)-treated and intact rats were used. Population spikes were recorded following Schaffer collateral stimulation. To induce LTP, primed burst tetanic stimulation was used. Paired-pulse stimulation at IPIs of 10, 20, 60, 120, 240, 360, and 480 ms were used and then EPI and PPI of CA1 were calculated. The results showed that the amplitude of population spike (PSA) increased 5, 15, 30, and 60 min after tetanic stimulation and 60 min after primed bursts, PSA increased at all stimulus intensities for all groups. In cysteamine-treated group, the magnitude of LTP was decreased as compared to intact and saline-treated groups. In the latter group, the magnitude of LTP Increased as compared to Intact and cysteamme- treated group. At IPI of 10 ms, mean value of EPI was greater than 1 for intact group and less than 1 for saline- and cysteamine-treated groups. In cysteamine-treated group, the mean value of EPI was significantly less than intact group. At IPIs from 20 to 480 ms, mean value of EPI was greater than or equal to I for all of the groups and no significant difference was observed among them. At IPI of 10 ms, mean value of PPI was greater than I in intact group and less than I in saline- and cysteamine-treated groups. In these groups, mean value of PPI was significantly less than intact group. At IPI of 20 ms, mean value of PPI was greater than I in intact and saline-treated group and less than I in cysteamine-treated group. In the latter group, the mean value of PPI was significantly less than saline-treated and intact groups. At IPIs of 60-680 ms, mean value of PPI was greater than I in all of the groups with no significant difference among them. It is concluded that cysteamine can alter susceptibility of hippocampal CA1 for synaptic plasticity induced by tetanic and paired-pulse paradigms.

In the present study, the effect of GABA (γ-aminobutyric acid) receptor agonists and antagonists on morphine-induced antinociception was investigated in formalin test in rats. Intraperitoneal (i.p.) injection of different doses of morphine (1, 3, 6 and 9 mg/kg) and intracerebroventricular (i.c.v.) injection of different doses of muscimol (0.5, 1 and 2 g/rat) or baclofen (0.25, 0.5 and 1 g/rat) induced a dose-dependent antinociception in both phases of formalin test. The responses induced by muscimol or baclofen in both phases reduced by bicuculline or CGP35348 respectively. Morphine in combination with different doses of muscimol or baclofen tends to elicit higher response. The opioid receptor antagonist reduced the response induced by both GABA receptor agonists. It can be concluded that stimulation of GABAA and GABAB receptors are responsible for antinociception in formalin test. However, at least part of the antinociception is due to the opioid receptor mechanism.

Ion channels are responsible for control of cell function in excitable tissues such as heart and brain and also in organs and tissues traditionally thought to be non- excitable including liver and epithelium. In the present research, the effect of lead (Pb2+) on Ca2+ -dependent action potential and currents was studied in F77 neuronal soma membrane of Helix aspersa. For this purpose, action potential generation and Ca2+ currents were investigated in the absence and presence of Pb2+ using two-electrode voltage clamp and current clamp methods. Two distinct types of high voltage activated (HVA) calcium currents were recorded. In this respect, one of them was sensitive to nifedipine (1 µM) and the other one was resistant to nifedipine. Extracellular application of Pb2+ at concentrations of 0.6 and 3 µM suppressed the firing behavior of F77 neurons. It also decreased the amplitude and the duration of calcium action potentials. The voltage clamp findings demonstrated that lead blocked more than 50% of HVA Ca2+ currents. The blocking effect of Pb2+ on Ca2+ was time-dependent. Therefore, it can be concluded that Pb2+ may alter the bioelectrical properties of F77 neuron through blocking high voltage activated Ca2+ currents, particularly L-type that are nifedipine sensitive.

The internal mammary artery (IMA) is currently the preferred conduit for myocardial revascularization. However, pre-operative vasospasm and a hypoperfusion state during maximal exercise may limit its use as a bypass graft. The mechanism of spasm has not been clearly defined. Since β-adrenoceptor activation plays a major role in vasorelaxation, the present study was carried out to investigate the β-adrenoceptor responsiveness of human IMA smooth muscle. For this purpose, IMA was obtained from patients with atherosclerosis of coronary artery whom have undergone coronary artery bypass. The endothelium-denuded rings of IMA were placed on platinum wires (L-shaped) in a Krebs solution containing tissue bath, and were connected to an isometric transducer. It was found out that Isoproterenol produced a dose-dependent relaxation in endothelium-denuded MA segments, precontracted with phenylephrine (maximal relaxation was 46.33 ± 5.45 %). Isoproterenol-induced relaxation was inhibited by atenolol (10-6 M) and proprano1ol (2 x 10-7 M). While atenolol-induced inhibition was partial, propranolol-induced inhibition was complete in a majority of the segments. BRL 37344, a selective 3-adrenoceptor agonist, produced a dose-dependent relaxation in phenylephrine pre contracted rings of endothelium-denuded IMA (maximal relaxation was 40.35 ± 4.07 %). Cyanopindolol, α-adrenoceptor partial agonist, produced a marked relaxation in endothelium-denuded IMA rings, precontracted with phenylephrine (maximal relaxation was 58.65 ± 6.2 %). Cyanopindolol-induced relaxation was resistant to blockade by propranolol (2 x 10-7 M). In addition, spontaneous contractions of IMA rings were observed in some of the cases that were inhibited by isoproterenol and BRL 37344. This observation may indicate the important role of β-adrenoceptor activation in prevention of human IMA spasm. Therefore, it is concluded that human IMA smooth muscle possesses both βl- and β2-adrenoceptors. The existence of β3-adrenoceptor in this tissue is also suggested.

The effect of chronic inflammation induced by complete Freund''s adjuvant (CFA) on anterior blood vessels of knee joint and its diameter was studied. Blood flow changes in response to phenylephrine (αl-adrenoceptor agonist) in CFA-treated and contralateral knee joints were observed over a 40-day period, using laser Doppler flowmetery (LDF) technique. Unilateral injection of CFA (0.2 ml) increased the diameter of injected knee at all days post-injection (p<0.001) and reached to its maximum level (49.7 ± 2%) at day 3. Then, the diameter decreased gradually but did not return to its initial value. In control animals, topical application of phenylephrine (10-13-10-17 M) to the exposed joint capsule decreased blood flow in a dose-dependent manner (11.1 ± 4.4 to 58.2 ± 4.5%, p<0.001). Unilateral injection of CFA attenuated the phenylephrine response in both ipsilateral and contralateral knees compared to the response of control animals (5.2 ± 1.6 to 48.3 ± 6.1% and 1.9 ± 2.2 to 45.3 ± 5.6 % respectively, p<0.05). The reduction persisted for three weeks after CFA injection (ipsilateral for 21 days; contralateral for 30 days, p<0.001). Then, the above response returned to its normal value. To evaluate the role of nitric oxide (NO) on the observed responses, amino guanidine (inducible-NO synthase inhibitor) was injected (120 mg/kg/day, i.p.) in other groups of CFA-treated animals. Arninoguanidine potentiated (p<0.001) the vasoconstrictor response to phenylephrine in both CFA injected and contralateral knees at 7, 14 and 21 days post-injection, and the increment of knee joint diameter was also less prominent. These findings may indicate that the vasoconstrictor response to phenylephrine is decreased in chronic inflammation, and increased production of NO during chronic inflammation might be involved.

There is strong evidence that two cerebral hemispheres are differentially involved in emotional memory and that amygdala is a key subcortical structure for emotional experience. The present research investigated the possible involvement of lateralization of basolateral amygdala (BLA) and central amygdala (CEA) in place avoidance memory. For this purpose, male Long-Evans rats (280-320 g) were implanted bilaterally with cannulae aimed at the BLA and CEA. One week later, the rats were trained in place avoidance apparatus as a spatial learning model. During the training session (30 min), the animal learned to avoid and recognize the places with a possibility of shock. One day later, bilateral or unilateral injection of TTX (5 ng/ml/side) were performed to inactivate temporarily the BLA and CEA during retrieval of the place avoidance task. Control rats were injected with the same volume of saline. Place avoidance training occurred in a single 30 min session and one day later, the avoidance memory was assessed during a 30 min extinction trial. The time to the first entrance and the number of entrances into the punished sector during extinction were used to measure the avoidance memory. The results indicated that bilateral or only right BLA inactivation significantly impaired retrieval of memory, although inactivation of the CEA and left BLA had no significant effect. Taken together, these results suggested that the right and left BLA make differential contribution to the expression of spatial memory and that the contribution of the right BLA may be more important.

It has been reported that neurons in the VL PAG projecting to nucleus raphe magnus (NRM) utilize excitatory amino acids as neurotransmitter. This projection plays an important role in the descending pain modulatory system. In order to determine the role of this pathway in pain perception, male rats received unilateral injection of ibotenic acid stereotaxically. For lesioning VL PAG, unilateral injection of ibotenic acid (0.2 and 0.5 µl) (a specific neurotoxin for EAA-containing neurons) was made. After a week recovery period, the nociception was evaluated using formalin test for a period of 60 min. At the end of experiments, animals were perfused by formaldehyde 10%. Serial sections (80 µm) wee prepared using vibratome. The sections were then Nissl stained and examined to determine the lesion location. The results revealed a significant increase in the first phase of formalin test. However, in the second phase, only 0.5 µl of the neurotoxin caused a significant decrease in pain perception. It is concluded that NMDA receptors within the PAG are involved in the perception of pain as measured in the formalin test.

In the present study, the effect of GABA (γ-aminobutyric acid) receptor agonists and antagonists on morphine-induced antinociception was investigated in formalin test in rats. Intraperitoneal (i.p.) injection of different doses of morphine (1, 3, 6 and 9 mg/kg) and intracerebroventricular (i.c.v.) injection of different doses of muscimol (0.5, 1 and 2 g/rat) or baclofen (0.25, 0.5 and 1 g/rat) induced a dose-dependent antinociception in both phases of formalin test. The responses induced by muscimol or baclofen in both phases reduced by bicuculline or CGP35348 respectively. Morphine in combination with different doses of muscimol or baclofen tends to elicit higher response. The opioid receptor antagonist reduced the response induced by both GABA receptor agonists. It can be concluded that stimulation of GABAA and GABAB receptors are responsible for antinociception in formalin test. However, at least part of the antinociception is due to the opioid receptor mechanism.