Physiology and Pharmacology
Volume:1 Issue: 1, 1997

Ketamine (KET) induced blockade of cortical spreading depression (CSD) declines with repeated KET applications in a way suggesting the development of tolerance. Possible mechanism of this process was studied in 31 rats anestheized with pentobarbital. CSD was elicited by injection of 1µl of 5% KCl into cortex at 15 min intervals and monitored by recording the accompanying slow potential waves. After control recording, five injections of KET (50 mg/kg) were applied at 75 min intervals. The first KET injection elicited CSD blockade lasting for 30-45 min at the near and for 60- 75 min at the far electrode. The CSD blocking effect of subsequent injections gradually declined and was not recognizable after the fifth KET injection. MK-801 (2 & 5 mg/kg) injected to rats with marked KET tolerance 30 min after the last KET dose, failed to block CSD. Without KET pretreatment the same dosage of MK-801 induced CSD blockade lasting more than 1 h. KET tolerance did not prevent local CSD blockade in cortical area superfused with 10 mol/l AP5. It is concluded that repeated applications of KET may induce some conformational changes at binding site(s) in the N-methyl-D-aspartate (NMDA) controlled channels shared by both KET and MK-801

The results of psychophysical studies suggest that displacement velocity may contribute significantly to the sensation of subcortical somatosensory neurons. The cortical correlates of these phenomena, however, are not known. In the present study the responses of rapidly adapting (RA) neurons in the forelimb region of cat primary somatosensory cortex (SI) to controlled displacement of skin and hair was studied. The cortical RA neurons were grouped according to their response patterns to constant-velocity ramp stimuli. Firing frequency, spontaneous activity, receptive field organization, and cortical laminar location of the RA neurons were studied and compared between the groups. There was a continuum in the response pattern of RA neurons to constant -velocity displacement. In one extent of the continuum, (G1IF1, n = 16) neurons typically responded to constant-velocity ramp stimuli with 1-3 impulses at the beginning of the ramp; they had little or no spontaneous activity and responded only to fast stimuli. In the other extent of the continuum, (G2IF2, n = 15) neurons responded throughout the ramp and sometimes during the initial phase of sustained stimuli. These neurons usually had higher spontaneous activities than G1IF1 neurons and responded to relatively slower stimuli. Gint/Fint (n = 18) neurons fell between the two types: they had an initial brief response which was sometimes followed, after a period of low or no activity, by a discharge towards the end of the ramp. Nine neurons had response patterns suggesting the existence of either convergence between these types or input from other types of mechanoreceptors. The average and instantaneous firing frequency of the majority of RA neurons increased as the ramp velocity was increased. The variation in the firing frequency of G2IF2 RA neurons had the widest range of firing frequencies and, in average, generated higher firing frequencies to both low and high displacement velocities. Coefficients of regression lines for linear, logarithmic and power functions were not significantly different among RA types. No correlation was found between cortical laminar location and RA types.

In the present study, the effects of different doses of nicotine on immobility time in mice were tested. Intraperitioneal administration of low doses of nicotine (0.025 mg/kg) decreased, but higher doses (0.8 and 1 mg/kg) increased immobility time. The anti-immobility response induced by low doses of nicotine was inhibited by high doses of the D2 receptor antagonist sulpiride, the central nicotinic receptor antagonist mecamylamine, reserpine and propranolol. The D1 receptor antagonist SCH 23390, the peripheral D2 receptor antagonist domperidone, hexamethonium, phenoxybenzamine and atropine did not alter nicotine effect. It can be concluded that the anti-immobility effect induced by low doses of nicotine is mediated by D2 dopamine receptor mechanism and possibly through a central nicotinic receptor stimulation.

Electrocochleography (ECoG) records the electrophysiologic activity of the most peripheral part of the auditory system, the inner ear cochlea and the 8th nerve. Auditory evoked potentials being recorded are Cochlear Microphonic (CM) and Summating Potential (AP). In order to provide the proper background for laboratory research and introducing an ECoG curve of a model animal, it was decided to record the ECoG from rabbit. Rabbits of either sex weighting about 2 kg (n=25) were experimented upon. Evoked auditory potentials to clicks of 75 and 85 dB were analyzed off-line and compared with human data obtained from a clinical audiometry laboratory. The results are as followed: -SP/AP amplitude and latency showed no significant difference in either intensities, in rabbit. -SP and AP amplitude and latency were significantly greater in rabbit. -The ratio of SP/AP amplitude and latency in rabbit and human indicated no differences. -AP amplitude in 75 dB intensity was greater in the right ear compared with the left (p ≤0.05); however, in other cases, amplitude of waves was greater in the left ear (p ≤0.05).

On most adrenergic and cholinergic nerve terminals, prejunctional α-adrenoceptors belonging to the α2-subtype have been identified. Activation of these receptors will decrease the release of norepinephrine. It has been reported that several isolated tissue preparations contain prejunctional dopamine receptors, the stimulation of which inhibits neurotransmission. It has remained uncertain whether the inhibition of cholinergic transmission in the smooth muscle of different tissues is mediated by prejunctional α-adrenoceptors or prejunctional dopaminoceptors. On the basis of these findings we aimed to examine the effects of dopamine and α-adrenergic receptor agonists on twitch response evoked by electrical stimulation of guinea pig common bile duct (CBD). Effects of various doses of bromocriptine and apomorphine, dopamine receptor agonists, on electrically evoked contractile responses of guinea pig CBD were investigated in this study. Bromocriptine and apomorphine produced a concentration -dependent reduction of the twitch heights. IC50 values for bromocriptine and apomorphine were 2.75 ± 0.715 x 10-6 M and 1.69 ± 0.l1 x 10-5 M, respectively. Pretreatment with sulpride, 0.1 and 1.0 µM prevented bromocriptine and apomorphine induced inhibition. PA2 values of sulpiride against bromocriptine and apomorphine were 8.26 and 6.29, respectively. Clonidine, 0.1 -100 µM, produced 49.3 ± 2.5% inhibition of twitch responses. Its effect was partially antagonized by yohimbine (l µM). It is concluded that both dopamine D2 and adrenergic α2 prejunctional receptors are present on the guinea-pig CBD cholinergic nerve and it seems that the role of dopamine D2-receptors is dominant. D2-dopaminoreceptor and α2-adrenoceptor agonists may relieve the biliary spasm.

In the present study, the effects of different doses of nicotine on immobility time in mice were tested. Intraperitioneal administration of low doses of nicotine (0.025 mg/kg) decreased, but higher doses (0.8 and 1 mg/kg) increased immobility time. The anti-immobility response induced by low doses of nicotine was inhibited by high doses of the D2 receptor antagonist sulpiride, the central nicotinic receptor antagonist mecamylamine, reserpine and propranolol. The D1 receptor antagonist SCH 23390, the peripheral D2 receptor antagonist domperidone, hexamethonium, phenoxybenzamine and atropine did not alter nicotine effect. It can be concluded that the anti-immobility effect induced by low doses of nicotine is mediated by D2 dopamine receptor mechanism and possibly through a central nicotinic receptor stimulation.

The effects of chronic morphine administration on the development of long-term potentiation (LTP) were investigated at the Schaffer collateral-CA1 pyramidal cell synapses of the rat hippocampal slices using primed-bursts tetanic stimulation. Significant enhancement of orthodromic population spike (OPS) was found for all stimulus intensities after tetanic stimulation. OPS enhancement was greatest when tested with low to mid-range stimulus intensities (25, 50 and 100 µ A). There was also significant decrease in OPS delay. These responses were similar in slices from both control and morphine dependent rats. At all delivered stimulus intensities, the amount of LTP of OPS in slices from dependent rats was larger than that of control slices. However, these differences in LTP of OPS were significant at low stimulus intensities. These findings suggest that chronic morphine administration had induced changes in CA1 neurocircuitry which modulated synaptic plasticity during high frequency stimulation and appeared as augmented LTP and also inhibition of LTP decay.

Iodine deficiency remains a major health problem in the world, including some parts of Iran. It has been recognized that there is usually a close and inverse relationship between iodine in the soil and water and presence of endemic goiter. Calcium has been suggested as one of goitrogens, though the definite role, extent and mechanism particularly in human have not been studied. Serum protein-bound iodine and urinary iodine excretion in male and female volunteers were investigated. To measure serum iodide concentration, blood samples were collected from 26 male and female subjects, with normal diet and two hours after consumption of calcium (10 mg/kg b.w.), iodine (5 µ g/kg b.w.) or iodine plus calcium. In another study carried out on 33 male and female volunteers, urinary iodine excretion during four different conditions was measured. The results indicate that high calcium intake with normal diet does not significantly effect serum protein-bound iodine concentrations, but high calcium intake plus iodine with normal diet can significantly increase serum protein-bound iodine concentrations. The result of this study, suggest that calcium significantly affects the iodine metabolism, when iodine intake is low.

TBS (Theta Burst Stimulation) and PBs (Primed Bursts) are among effective tetanic stimulations for induction of LTP in hippocampus. Recent studies have indicated that TBS is effective in LTP induction in layer III synapses of neocortex, only if applied to layer IV. However, the possibility of neocortical LTP induction using PBs, has not yet been investigated. Sensory deprivation greatly influences the development of neocortex. Based on the effect of sensory deprivation on synaptic plasticity of developing neocortex, the induction of LTP by PBs in visual cortical slices of control and dark-reared rats, was studied. Results obtained show that application of PBs to layer IV, could effectively induce LTP. Field potential recordings consisted of two components; pEPSPl and pEPSP2. In most cases PBs lead to selective potentiation of pEPSP2. Visual deprivation increased the incidence of LTP of pEPSP2 and also increased the incidence of LTD of pEPSP2. These findings show that PBs could be used as an effective tetanic stimulation to study the synaptic plasticity in neocortex. The effects of visual deprivation on LTP/LTD are consistent with its role on the development of NMDA system in neocortex.

Recently, vast studies have been focused on the antinociceptive and anesthetic effects of α2 adrenergic receptors, using specific drugs such as medetomidine and dexmedetomidine. In the present study, we tried to assess the peripheral and central effects of dexmedetomidine in phasic and tonic pain, on rats, using tail flick and formalin tests. Dexmedetomidine, administered intraperitoneally (25, 50 and 100 µg/kg, i.p.) or intracerebroventrically (7.5, 10 and 20 µg, i.c.v.) induced total anesthesia. This effect could be seen by 10 and 20 µg, i.c.v. doses of the drug in spinal animals, too, which was reversed by 5 µg, i.c.v. of yohimbine. Dexmedetomidine (6.5 µg, i.c.v. or 20 µg, i.p.) showed antinociceptive effects in formalin test which was reversed by yohimbine (5 µg, i.c.v.). Dexmedetomidine (5, 6.5, 7.5, 10 and 20 µg, i.c.v. or 20, 25, 50 and 100 µg/kg, i.p.) had significant antinociceptive effects in tail flick test, which could be reversed by 5 µg, i.c.v. administration of yohimbine. The results of tail flick test in the spinal animals, shows that dexmedetomidine (6 µg, i.c.v.) in these animals induces antinociception, which was reversed by yohimbine pretreatment (1 mg/kg, i.p.). These results indicate that, dexmedetomidine probably exerts, its antinociceptive effect, through spinal α2 adrenergic receptors.