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ABSTRACT: The neurosteroid pregnenolone sulfate (PS), a representative excitatory neuromodulator, has a variety of neuropharmacological actions, such as memory enhancement and convulsant effects. In this study, the effects of PS on glycinergic transmission, such as glycinergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs), were investigated in acutely isolated medullary dorsal horn neurons by use of a conventional whole-cell patch-clamp technique. PS significantly increased the frequency but decreased the amplitude of glycinergic mIPSCs in a concentration-dependent manner. PS also accelerated the decay time constant of glycinergic mIPSCs. The PS-induced decrease in mIPSC amplitude was due to the direct postsynaptic inhibition of glycine receptors because PS inhibited the glycine-induced Cl- currents in a noncompetitive manner. The PS-induced increase in mIPSC frequency was not due to the activation of α7 nicotinic acetylcholine, NMDA, σ1 receptors and voltage-dependent Ca(2+) channels, which are known to be molecular targets of PS. On the other hand, the PS-induced increase in mIPSC frequency was completely attenuated either in the Ca(2+)-free external solution or in the presence of transient receptor potential (TRP) channel blockers, suggesting that PS elicits an increase in Ca(2+) concentration within glycinergic nerve terminals, via the activation of putative TRP channels. The PS-mediated modulation of glycinergic synaptic transmission, such as the enhancement of presynaptic glycine release and direct inhibition of postsynaptic glycine receptors, might have a broad impact on the excitability of medullary dorsal horn neurons and therefore affect the processing of nociceptive transmission from orofacial tissues.
European journal of pharmacology 05/2013; · 2.59 Impact Factor
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ABSTRACT: Histaminergic neurons within the tuberomammillary nucleus (TMN) play an important role in the regulation of sleep-wakefulness. Here, we report the adrenergic modulation of GABAergic transmission in rat TMN histaminergic neurons using a conventional whole-cell patch clamp technique. Norepinephrine (NE) reversibly decreased the amplitude of action potential-dependent GABAergic inhibitory postsynaptic currents (IPSCs) and increased the paired-pulse ratio. The NE-induced inhibition of GABAergic IPSCs was mimicked by clonidine, a selective α2 adrenoceptor agonist. However, cirazoline and isoproterenol, nonselective α1 and β adrenoceptor agonists, respectively, had no effect on GABAergic IPSCs. The NE-induced inhibition of GABAergic IPSCs was significantly blocked by BRL44408, a selective α2A adrenoceptor antagonist, but not imiloxan or JP1302, a selective α2B and α2C adrenoceptor antagonists. The extent of NE-induced inhibition of GABAergic IPSCs was inversely proportional to the extracellular Ca(2+) concentration. Pharmacological agents affecting the activities of adenylyl cyclase or G-protein coupled inwardly rectifying K(+) channels did not affect the NE-induced inhibition of GABAergic IPSCs. However, NE had no effect on the frequency and amplitude of GABAergic miniature IPSCs. These results suggest that NE acts on presynaptic α2A adrenoceptor to inhibit action potential-dependent GABA release via the inhibition of Ca(2+) influx from the extracellular space to GABAergic nerve terminals, and that this α2A adrenoceptor-mediated modulation of GABAergic transmission may be involved in regulating the excitability of TMN histaminergic neurons. This article is protected by copyright. All rights reserved.
Journal of Neurochemistry 04/2013; · 4.06 Impact Factor
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ABSTRACT: Electroencephalographic (EEG) activities reflect the functional state of the brain, but it is difficult to objectively describe functional brain states. Here, we describe two statistical divergence measures, Mahalanobis distance and Hellinger distance of projections to the reference spaces, to evaluate their state-discriminating ability. Last, divergence measures of 30-min segments after caffeine treatment were compared to evaluate the dose- and time-dependent arousal effects of caffeine to the best reference space. EEG was recorded from Sprague-Dawley rats during pre- and post-administration of caffeine. Several two-dimensional reference spaces were constructed from subsets of the normalized 7 relative band powers pooled from the pre-drug period of all recordings for each cortex: two reference spaces from data sets of the frontal and parietal cortex, and four reference spaces from data sets of active wake, slow-wave sleep, paradoxical sleep state, and all states. Sleep-wake states used as test states were plotted onto the reference spaces, and then, two divergence measures were derived to measure state-discriminating ability of each reference space. First, the reference space of the same cortex as test data was better for discriminating test states than another cortical reference space. Second, the one reference space constructed from data of all states was better for discriminating test states than the other reference spaces. Third, divergence measures were well correlated with sleep-wake durations after caffeine administration and showed the temporal trends of caffeine-induced arousal effect. These results suggest that two statistical measures can objectively describe brain functional states and drug-induced states.
Journal of neuroscience methods 08/2012; 211(1):40-8. · 2.30 Impact Factor
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ABSTRACT: We studied the effects of acetylcholinesterase inhibitors, donepezil and galantamine, and an N-methyl-D-aspartate (NMDA) receptor blocker, memantine, on sleep-wake architecture in rats. Screw electrodes were chronically implanted into the frontal and parietal cortex for the electroencephalography (EEG). EEG was recorded with a bio-potential amplifier for 8 h from 09:30 to 17:30. Vibration was recorded to monitor animal activity with a vibration measuring device. Sleep-wake states such as wake (W), slow-wave sleep (S) and paradoxical or rapid eye movement sleep (P), were scored every 10 sec by an experimenter. We measured mean episode duration and number of episode to determine which factor sleep disturbance was attributed to. Donepezil and memantine showed a significant increase in total W duration and decreases in total S and P duration and delta activity. Memantine showed increases in sleep latency and motor activity. Changes of S and P duration in memantine were attributed from changes of mean episode duration. Galantamine had little effect on sleep architecture. From these results, it is showed that galantamine may be an anti-dementia drug that does not cause sleep disturbances and memantine may be a drug that causes severe sleep disturbance.
Korean Journal of Physiology and Pharmacology 08/2012; 16(4):231-6. · 0.96 Impact Factor
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ABSTRACT: Jaceosidin is a naturally occurring flavone with pharmacological activity. Jaceosidin, as one of the major constituents of the medicinal herbs of the genus Artemisia, has been shown to exert anticancer, anti-oxidative, anti-inflammatory, and immunosuppressive effects. This study was undertaken to determine the effect of jaceosidin on microglia and neuroinflammation. Microglia are the innate immune cells in the central nervous system, and they play a central role in the initiation and maintenance of neuroinflammation. We report that jaceosidin inhibits inflammatory activation of microglia, reducing nitric oxide (NO) production and proinflammatory cytokine expression. IC(50) for NO inhibition was 27 ± 0.4 μM. The flavone also attenuated microglial neurotoxicity in the microglia/neuroblastoma co-culture. Systemic injection of jaceosidin ameliorated neuroinflammation in the mouse model of experimental allergic encephalomyelitis. These results indicate that plant flavone jaceosidin is a microglial inhibitor with anti-neuroinflammation activity. Copyright © 2012 John Wiley & Sons, Ltd.
Phytotherapy Research 05/2012; · 2.09 Impact Factor
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ABSTRACT: L-theanine has been reported to inhibit the excitatory effects of caffeine. The present study examined the effects of L-theanine on caffeine-induced sleep disturbances in rats. Rats received the following drug pairings: saline and saline (Control), 7.5 mg/kg caffeine and saline, or 7.5 mg/kg of caffeine followed by various doses of L-theanine (22.5, 37.5, 75, or 150 mg/kg). Vigilance states were divided into: wakefulness (W), transition to slow-wave sleep (tSWS), slow-wave sleep (SWS), and rapid-eye-movement sleep (REMS). Caffeine significantly increased the duration of W and decreased the duration of SWS and REMS compared to the Control. Although L-theanine failed to reverse the caffeine-induced W increase, at 22.5 and 37.5 mg/kg (but not at 75 and 150 mg/kg), it significantly reversed caffeine-induced decreases in SWS. In conclusion, low doses of L-theanine can partially reverse caffeine-induced reductions in SWS; however, effects of L-theanine on caffeine-induced insomnia do not appear to increase dose-dependently.
Pharmacology Biochemistry and Behavior 04/2012; 101(2):217-21. · 2.53 Impact Factor
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ABSTRACT: Amitriptyline, a representative tricyclic antidepressant, has been widely used for the treatment of neuropathic pain, such as post-herpetic and trigeminal neuralgia. In the present study, we investigated the effect of amitriptyline on glycinergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in acutely isolated medullary dorsal horn neurons by use of a conventional whole-cell patch-clamp technique. Amitriptyline (30 μM) significantly increased mIPSC frequency without affecting the current amplitude, suggesting that amitriptyline acts presynaptically to increase the probability of glycine release. Amitriptyline also directly inhibited the glycine receptor-mediated Cl(-) currents induced by lower concentrations of glycine. The amitriptyline-induced increase in mIPSC frequency was not affected either in the Na(+)-free external solutions or in the presence of Cd(2+), a general voltage-dependent Ca(2+) channel blocker, indicating that amitriptyline is unlikely to elicit a presynaptic depolarization. In addition, amitriptyline still increased mIPSC frequency even in the absence of extracellular Ca(2+). In contrast, the depletion of intracellular Ca(2+) stores with thapsigargin significantly reduced the extent of amitriptyline-induced increase in mIPSC frequency. These data suggest that amitriptyline increases spontaneous glycine release onto acutely isolated medullary dorsal neurons by increasing the intraterminal Ca(2+) concentration, which might be mediated by the Ca(2+) release from the Ca(2+) stores rather than the Ca(2+) influx from the extracellular space. The amitriptyline-induced modulation of glycinergic transmission could have a broad impact on the excitability of medullary dorsal neurons, and this mechanism would contribute, at least in part, to the anti-allodynic action of amitriptyline.
Brain research 03/2012; 1455:10-8. · 2.46 Impact Factor
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ABSTRACT: We have recently reported that tyramine acts on putative presynaptic trace amine receptors to inhibit glycinergic transmission in substantia gelatinosa (SG) neurons of the rat trigeminal subnucleus caudalis. However, it is still unknown how tyramine elicits presynaptic inhibition of glycine release. In the present study, therefore, we investigated cellular mechanisms underlying the tyramine-induced inhibition of glycinergic transmission in SG neurons using a conventional whole-cell patch clamp technique. Tyramine (100 μM) reversibly and repetitively decreased the amplitude of action potential-dependent glycinergic inhibitory postsynaptic currents (IPSCs), and increased the paired-pulse ratio. Pharmacological data suggest that the tyramine-induced decrease in glycinergic IPSCs was not mediated by the modulation of adenylyl cyclase, protein kinase A and C, or G-protein coupled inwardly rectifying K(+) channels. On the other hand, glycinergic IPSCs were mainly mediated by the Ca(2+) influx passing through presynaptic N-type and P/Q-type Ca(2+) channels. The tyramine-induced decrease in glycinergic IPSCs was completely blocked by ω-conotoxin GVIA, an N-type Ca(2+) channel blocker, but not ω-agatoxin IVA, a P/Q-type Ca(2+) channel blocker. The results suggest that tyramine acts presynaptically to decrease action potential-dependent glycine release onto SG neurons via the selective inhibition of presynaptic N-type Ca(2+) channels. This tyramine-induced inhibition of glycinergic transmission in SG neurons might affect the process of orofacial nociceptive signals.
European journal of pharmacology 08/2011; 664(1-3):29-35. · 2.59 Impact Factor
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ABSTRACT: Although quantitative EEG parameters, such as spectral band powers, are sensitive to centrally acting drugs in dose- and time-related manners, changes of the EEG parameters are redundant. It is desirable to reduce multiple EEG parameters to a few components that can be manageable in a real space as well as be considered as parameters representing drug effects. We calculated factor loadings from normalized values of eight relative band powers (powers of 0.5, 1.0~2.0, 2.5~4.0, 4.5~5.5, 6.0~8.0, 8.5~12.0, 12.5~24.5, and 25~49.5 Hz bands expressed as ratios of the power of 0.5-49.5 Hz band) of EEG during pre-drug periods (11:00~12:00) by factor analysis and constructed a two-dimensional canonical space (reference canonical space) by canonical correlation analysis. Eight relative band powers of EEG produced by either physostigmine or yohimbine were reduced to two canonical scores in the reference canonical space. While changes of the band powers produced by physostigmine and yohimbine were too redundant to describe the difference between two drugs, locations of two drugs in the reference canonical space represented the difference between two drug's effects on EEG. Because the distance between two locations in the canonical space (Mahalanobis distance) indicates the magnitude of difference between two different sets of EEG parameters statistically, the canonical scores and the distance may be used to quantitatively and qualitatively describe the dose-dependent and time-dependent effects and also tell similarity and dissimilarity among effects. Then, the combination of power spectral analysis and statistical analysis may help to classify actions of centrally acting drugs.
Experimental neurobiology. 03/2011; 20(1):54-65.
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ABSTRACT: 3α-Hydroxy, 5α-reduced pregnane steroids, such as allopregnanolone, are potent modulators of GABA(A) receptors and have many biological responses including sedative, anxiolytic, anticonvulsant and anesthetic actions. In the present study, we have investigated the effects of allopregnanolone on GABA(A) receptors in acutely isolated single hippocampal CA3 pyramidal neurons using the whole cell patch-clamp technique. Allopregnanolone induced membrane Cl(-) currents in a concentration-dependent manner, and the allopregnanolone-induced currents (I(AlloP)) were blocked by noncompetitive GABA(A) receptor antagonists. The I(AlloP) was not affected by the intracellular loading of γ-cyclodextrin (γ-CD), which efficiently sequesters several kinds of endogenous neurosteroids including allopregnanolone, suggesting that allopregnanolone accesses extracellular but not intracellular sites to activate GABA(A) receptors. Allopregnanolone prolonged the decay time constant of GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs), suggesting that allopregnanolone modulates the desensitization kinetics of postsynaptic GABA(A) receptors. The picrotoxin-sensitive tonic currents (I(tonic)), which were mediated by extrasynaptic GABA(A) receptors, were recorded from CA3 pyramidal neurons. The intracellular loading of γ-CD or allopregnanolone significantly decreased or increased the amplitude of picrotoxin-sensitive I(tonic), respectively, suggesting that endogenous neurosteroids might, at least in part, be involved in the generation of picrotoxin-sensitive I(tonic). Allopregnanolone also increased the frequency of GABAergic sIPSCs, in a manner dependent on the integrity of voltage-dependent Na(+) and Ca(2+) channels, suggesting that allopregnanolone activates presynaptic GABA(A) receptors to depolarize GABAergic nerve terminals. The present results suggest that allopregnanolone exerts its pharmacological and pathophysiological actions via the modulation of multiple types of GABA(A) receptor-mediated responses.
European journal of pharmacology 02/2011; 652(1-3):46-54. · 2.59 Impact Factor
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ABSTRACT: The sleep homeostatic response significantly affects the state of anesthesia. In addition, sleep recovery may occur during anesthesia, either via a natural sleep-like process to occur or via a direct restorative effect. Little is known about the effects of isoflurane anesthesia on sleep homeostasis. We investigated whether 1) isoflurane anesthesia could provide a sleep-like process, and 2) the depth of anesthesia could differently affect the post-anesthesia sleep response. Nine rats were treated for 2 hours with ad libitum sleep (Control), sleep deprivation (SD), and isoflurane anesthesia with delta-wave-predominant state (ISO-1) or burst suppression pattern-predominant state (ISO-2) with at least a 1-week interval. Electroencephalogram and electromyogram were recorded and sleep-wake architecture was evaluated for 4 hours after each treatment. In the post-treatment period, the duration of transition to slow-wave-sleep decreased but slow wave sleep (SWS) increased in the SD group, but no sleep stages were significantly changed in ISO-1 and ISO-2 groups compared to Control. Different levels of anesthesia did not significantly affect the post-anesthesia sleep responses, but the deep level of anesthesia significantly delayed the latency to sleep compared to Control. The present results indicate that a natural sleep-like process likely occurs during isoflurane anesthesia and that the post-anesthesia sleep response occurs irrespective to the level of anesthesia.
Korean Journal of Physiology and Pharmacology 10/2010; 14(5):291-7. · 0.96 Impact Factor
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ABSTRACT: Ginsenoside Rb1, a major ingredient of ginseng saponins, can affect various brain functions, including learning and memory. When ingested orally, ginsenoside Rb1 is not found in plasma as well as urine, but its metabolite compound K (ComK) reaches the systemic circulation in animals and human. Nevertheless, the pharmacological actions of ComK are still poorly known. In the present study, we investigated the effect of ComK on GABAergic spontaneous miniature inhibitory post-synaptic currents (mIPSCs) in acutely isolated rat hippocampal CA3 pyramidal neurons using a conventional whole-cell patch-clamp technique. While ComK significantly increased mIPSC frequency in a concentration-dependent manner, it had no effect on the current amplitude, suggesting that ComK acts pre-synaptically to increase the probability of spontaneous GABA release. ComK still increased mIPSC frequency even in a Ca(2+) -free external solution, suggesting that the ComK-induced increase spontaneous GABA release is not related to Ca(2+) influx from the extracellular space. However, the ComK-induced increase mIPSC frequency was significantly decreased after the blockade of either sarcoplasmic/endoplasmic reticulum Ca(2+) -ATPase or Ca(2+) release channels. These results strongly suggest that ComK enhances spontaneous GABA release by increasing intraterminal Ca(2+) concentration via Ca(2+) release from pre-synaptic Ca(2+) stores. The ComK-induced modulation of inhibitory transmission onto CA3 pyramidal neurons could have a broad impact on the excitability of CA3 pyramidal neurons and affect the physiological functions mediated by the hippocampus.
Journal of Neurochemistry 08/2010; 114(4):1085-96. · 4.06 Impact Factor
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ABSTRACT: Operant conditioning is often used to train a desired behavior in an animal. The contingency between a specific behavior and a reward is required for successful training. Here, we compared the effectiveness of two different mazes for training turning behaviors in response to directional cues in Sprague-Dawley rats. Forty-three rats were implanted with electrodes into the medial forebrain bundle and the left and right somatosensory cortices for reward and cues. Among them, thirteen rats discriminated between the left and right somatosensory stimulations to obtain rewards. They were trained to learn ipsilateral turning response to the stimulation of the left or right somatosensory cortex in either the T-maze (Group T) or the E| maze (Group W). Performance was measured by the navigation speed in the mazes. Performances of rats in Group T were enhanced faster than those in Group W. A significant correlation between performances during training and performance in final testing was observed in Group T starting with the fifth training session while such a correlation was not observed in Group W until the tenth training session. The training mazes did not however affect the performances in the final test. These results suggest that a simple maze is better than a complicated maze for training animals to learn directions and direct cortical stimulation can be used as a cue for direction training.
Behavioural processes 07/2010; 84(3):715-20. · 1.53 Impact Factor
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ABSTRACT: The effects of different doses of tramadol on analgesia and electroencephalographic (EEG) spectral parameters were compared in rats. Saline or tramadol 5, 10, 20 or 40 mg/kg was administered. The degree of analgesia was evaluated by tail-flick latency, and the degree of seizure was measured using numerical seizure score (NSS). Additionally, band powers, median power frequency and spectral edge frequency 95 were measured to quantify the EEG response. All doses of tramadol produced spike-wave discharge. Tramadol significantly and dose-dependently increased the analgesia, but these effects did not correspond with the changes in the EEG spectral parameters. NSS significantly increased in the Tramadol 20 and 40 mg/kg treatment groups compared to the Control and TRA5 groups, and two rats given 40 mg/kg had convulsions. In conclusion, tramadol dose-dependently increased the analgesic effect, and the 10 mg/kg dose appears to be a reliable clinical dose for analgesia in rats, but dose-dependent increases in analgesia and seizure severity did not correlate with EEG spectral parameters.
Korean Journal of Physiology and Pharmacology 06/2010; 14(3):191-8. · 0.96 Impact Factor
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ABSTRACT: To investigate the effects of atipamezole administered before butorphanol, on tail-flick latency (TFL) and also following medetomidine-ketamine anaesthesia in rats.
Prospective, randomized experimental study.
Thirty-four adult male Sprague-Dawley rats weighing 260-390 g.
TFL in 50 degrees C water was used to measure antinociception. In the first experiment, rats received saline (n = 5) or atipamezole (n = 5) followed by butorphanol treatments. In the second experiment, three groups of rats received saline (n = 8), atipamezole (n = 8) or atimpamezole (n = 8) followed by butorphanol 60 minutes after medetomidine-ketamine administration.
In the first experiment, butorphanol significantly increased TFL compared to baseline. Atipamezole significantly decreased this effect. In the second experiment, TFL was significantly increased after recovery from medetomidine-ketamine anaesthesia compared to baseline. This was almost completely blocked by atipamezole. Atipamezole with butorphanol after recovery from the anaesthesia significantly reduced TFL compared to saline but still significantly increased TFL compared to the baseline.
Atipamezole attenuated the analgesic effects of butorphanol. When postoperative atipamezole is used to hasten recovery from anaesthesia in rats, it may interfere with the postoperative analgesic effect of butorphanol.
Veterinary Anaesthesia and Analgesia 11/2009; 36(6):591-6. · 0.94 Impact Factor
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ABSTRACT: To compare the anaesthetic effects of varying doses of medetomidine (MED) combined with ketamine (KET) in rats, and to determine the efficacy of atipamezole (ATI) in the reversal of these effects using electroencephalogram (EEG) and assessment of clinical parameters.
Prospective, randomized experimental trial.
Twenty-one male Sprague-Dawley rats weighing 300-398 g and aged 8-11 weeks old.
Three groups received intraperitoneal injections of MED (0.2, 0.4 or 0.8 mg kg(-1)) with KET (60 mg kg(-1)) (MED-200, MED-400 and MED-800). Atipamezole, at doses five times higher than the previous dose of MED, was then administered intraperitoneally 70 minutes after MED-KET injection. The EEG band powers and spectral edge frequencies (SEFs), respiratory rates, reflex scores to toe-web clamping and behavioural changes were measured. Correlations between EEG parameters and reflex scores were also evaluated.
The duration of surgical anaesthesia was directly proportional to the dose of MED. Lower frequency bands (delta 1 to alpha2) increased in all groups, and these changes were reversed by ATI. Minimal changes were observed in the higher frequency bands (beta1 to gamma), but their powers were increased by ATI. The SEFs were decreased in all groups, and they were reversed by ATI. While alpha1 band power and SEF95 showed strong correlations with the depth of anaesthesia, their changes appeared before the measured decreases in reflex score. Recovery from anaesthesia was extended by increasing the dose of MED.
Spectral EEG parameters may not accurately predict the depth of surgical anaesthesia because they had already changed during the induction of surgical anaesthesia. The ATI dose used in the present study may not be enough for complete reversal of anaesthesia induced by MED-KET.
Veterinary Anaesthesia and Analgesia 08/2009; 36(4):319-27. · 0.94 Impact Factor
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ABSTRACT: To compare the effect of three different administration rates of one dose of propofol on the depth and duration of anaesthesia and cardiopulmonary function during induction of anaesthesia in rats using electroencephalogram (EEG) and clinical signs.
Prospective, randomized experimental trial. Animals Twenty-one, adult, male Sprague-Dawley rats weighing 341 +/- 26 g (mean +/- SD) (325 to 480 g).
were randomly divided into three groups to receive 20 mg kg(-1) propofol as a bolus injection over 1, 2 or 3 minutes (groups P1, P2 and P3 respectively) intravenously (IV). The total duration and number of burst suppression (BS) episodes in the EEG, the time to loss of righting reflex, reflex score from electrical stimulation, respiratory rate, mean arterial pressure and pulse rate were measured from the beginning of propofol injection.
While loss of reflex to electrical stimulus and time to loss of righting reflex in group P3 were slower than in other groups, the total duration and number of BS episodes in group P3 were significantly higher than in groups P1 and P2 and cardiopulmonary depression was less prominent in group P3 than in groups P1 and P2 up to 2 minutes after the start of administration.
Twenty milligram per kg propofol administration IV for 3 minutes increased the duration of anaesthesia and decreased cardiopulmonary depression in rats.
Slower infusion of propofol produced surgical anaesthesia with less cardiopulmonary depression in rats.
Veterinary Anaesthesia and Analgesia 06/2009; 36(3):239-45. · 0.94 Impact Factor
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ABSTRACT: Repeated psychostimulants induce electroencephalographic (EEG) changes, which reflect adaptation of the neural substrate related to dopaminergic pathways. To study the role of dopamine receptors in EEG changes, we examined the effect of apomorphine, the dopamine D1 receptor antagonist, SCH-23390, and the D2 receptor antagonist, haloperidol, on EEG in rats. For single and repeated apomorphine treatment groups, the rats received saline or apomorphine for 4 days followed by a 3-day withdrawal period and then apomorphine (2.5 mg/kg, i.p.) challenge after pretreatment with saline, SCH-23390, or haloperidol on the day of the experiment. EEGs from the frontal and parietal cortices were recorded. On the frontal cortex, apomorphine decreased the power of all the frequency bands in the single treatment group, and increased the theta (4.5~8 Hz) and alpha (8~13 Hz) powers in the repeated treatment group. Changes in both groups were reversed to the control values by SCH-23390. On the parietal cortex, single apomorphine treatment decreased the power of some frequency bands, which were reversed by haloperidol but not by SCH-23390. Repeated apomorphine treatment did not produce significant changes in the power profile. These results show that adaptation of dopamine pathways by repeated apomorphine treatment could be identified with EEG changes such as increases in theta and alpha power of the frontal cortex, and this adaptation may occur through changes in the D1 receptor and/or the D2 receptor.
Korean Journal of Physiology and Pharmacology 06/2009; 13(3):147-51. · 0.96 Impact Factor
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ABSTRACT: Although it has been well established that GABA(A) receptors are molecular targets of a variety of allosteric modulators, such as benzodiazepines, the pharmacological properties of presynaptic GABA(A) receptors are poorly understood. In this study, the effects of diazepam and Zn(2+) on presynaptic GABA(A) receptors have been investigated by measuring the GABA(A) receptor-mediated facilitation of spontaneous glutamate release in mechanically dissociated rat CA3 pyramidal neurons. Diazepam significantly enhanced the muscimol-induced facilitation (particularly at submicromolar concentrations) of spontaneous glutamate release and shifted the concentration-response relationship for muscimol toward the left, whereas Zn(2+) (<OR= 100 muM) had little effect on the muscimol-induced facilitation of spontaneous glutamate release. In contrast, Zn(2+) significantly suppressed the muscimol-induced currents mediated by GABA(A) receptors expressed on dentate gyrus granule cells, which are parent neurons of mossy fibers, whereas the effect of diazepam on GABA(A) receptors expressed on dentate gyrus granule cells was lesser than that on presynaptic GABA(A) receptors. The results suggest that the pharmacological properties of GABA(A) receptors differ considerably between presynaptic (axon terminals) and somatic regions in the same granule cell and that presynaptic GABA(A) receptors should be considered as one of the important pharmacological targets of many drugs affecting GABA(A) receptors.
Journal of Neurochemistry 05/2009; 109(4):995-1007. · 4.06 Impact Factor
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ABSTRACT: Although glycine receptors are found in most areas of the brain, including the hippocampus, their functional significance remains largely unknown. In the present study, we have investigated the role of presynaptic glycine receptors on excitatory nerve terminals in spontaneous glutamatergic transmission. Spontaneous EPSCs (sEPSCs) were recorded in mechanically dissociated rat dentate hilar neurons attached with native presynaptic nerve terminals using a conventional whole-cell patch recording technique under voltage-clamp conditions. Exogenously applied glycine or taurine significantly increased the frequency of sEPSCs in a concentration-dependent manner. This facilitatory effect of glycine was blocked by 1 microM strychnine, a specific glycine receptor antagonist, but was not affected by 30 microM picrotoxin. In addition, Zn(2+) (10 microM) potentiated the glycine action on sEPSC frequency. Pharmacological data suggested that the activation of presynaptic glycine receptors directly depolarizes glutamatergic terminals resulting in the facilitation of spontaneous glutamate release. Bumetanide (10 microM), a specific Na-K-2C co-transporter blocker, gradually attenuated the glycine-induced sEPSC facilitation, suggesting that the depolarizing action of presynaptic glycine receptors was due to a higher intraterminal Cl(-) concentration. The present results suggest that presynaptic glycine receptors on excitatory nerve terminals might play an important role in the excitability of the dentate gyrus-hilus-CA3 network in physiological and/or pathological conditions.
Journal of Neurochemistry 03/2009; 109(1):275-86. · 4.06 Impact Factor
