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Paul F Smith - One of the best experts on this subject based on the ideXlab platform.
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the effects of long term low dose diazepam treatment on the guinea pig Righting Reflex and medial vestibular nucleus neuronal activity
Pharmacology Biochemistry and Behavior, 1995Co-Authors: Mark A Hutchinson, Cynthia L Darlington, Paul F SmithAbstract:Abstract Guinea pigs received a 2 mg/kg IP injection of diazepam, or an equivalent volume of vehicle, daily for 28–60 days. To determine whether tolerance developed to the ataxic effects of diazepam on the Righting Reflex, daily Righting Reflex latency (RRL) measurements were made before and 20, 30, and 40 min following the diazepam or vehicle injection for 28 days. Analyses of the RRLs for individual animals indicated that a significant decrease in RRL over time (indicating tolerance) occurred in only one out of nine animals receiving diazepam and in none of the vehicle animals. Medial vestibular nucleus (MVN) neurons in brain stem slices from animals receiving chronic diazepam treatment had a significantly higher average firing rate than those from vehicle controls. These results suggest that: a) long-term treatment with single 2 mg/kg daily IP injections of diazepam does not result in tolerance to diazepam's ataxic effects on the Righting Reflex in the majority of animals; b) this form of diazepam treatment may, nonetheless, induce a hyperactivity of brain stem MVN neurons that may be consistent with the occurrence of a withdrawal syndrome.
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quantification of the depressive effects of diazepam on the guinea pig Righting Reflex
Pharmacology Biochemistry and Behavior, 1994Co-Authors: Sarah J Scott, Paul F Smith, Cynthia L DarlingtonAbstract:The effects of 5 mg/kg/day diazepam (IP for 21–39 days) on Righting Reflex latency (RRL) and neuronal activity in the medial vestibular nucleus (MVN) were investigated in guinea pigs. Diazepam treatment increased the RRL relative to vehicle-injected controls (p < 0.05, ANOVA); although the average RRL in the diazepam-treated animals did decrease over time, this decrease was not statistically significant and therefore evidence of tolerance was not obtained. MVN slices were removed from diazepam-treated animals and recordings were made from MVN neurons in vitro. The average resting activities for MVN neurons in slices from diazepam-treated animals and uninjected animals from a previous study were not significantly different.
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the tolerometer a fast automated method for the measurement of Righting Reflex latency in chronic drug studies
Journal of Neuroscience Methods, 1993Co-Authors: Barry Dingwall, Bradley Reeve, Paul F Smith, Mark A Hutchinson, Cynthia L DarlingtonAbstract:We describe a fast, automated system for the measurement of Righting Reflex latencies in drug studies. This system, which we call a “tolerometer”, is especially useful for studies of drug tolerance which require a simple measurement of motor behaviour on a daily basis, for long periods of time. The tolerometer consists of a semi-cylindrical platform positioned on a 2 kg load cell, connected to a strain gauge amplifier (Radio Spares Ltd). The output from the amplifier is connected to a MacLab data acquisition system (Analog Digital Instruments), controlled by a Macintosh Classic computer. The MacLab Chart program is used to display, on the Macintosh screen, the load changes which occur during a Righting Reflex; sampling frequencies up to 40 kHz can be used, but we find 20–100 Hz adequate. Using measurement cursors provided by the Chart program, the latency from the point at which an animal is placed on the tolerometer platform in the supine position, until the completion of a Righting Reflex, can be measured accurately and easily.
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simple device for quantifying drug effects on the Righting Reflex
Pharmacology Biochemistry and Behavior, 1992Co-Authors: Bradley Reeve, Barry Dingwall, Cynthia L Darlington, Sarah J Scott, Andrew J Sansom, Paul F SmithAbstract:Abstract A simple, inexpensive device is described that allows quantification of the effects of drugs on the Righting Reflex. This device consists of a modified set of kitchen scales connected to a digital timer. Two moveable Hall effect switches are positioned around the pointer, which registers the weight of the animal on the scales; when the animal is placed on the scales in the supine position, the initiation of a Righting Reflex causes the pointer to cross one of the switches, stopping the digital timer and providing a measure of Righting Reflex latency (RRL). We describe an efficient protocol for using this device that provides quantification of drug effects on the RRL, which can then be subjected to analysis using parametric statistics such as analysis of variance.
Cynthia L Darlington - One of the best experts on this subject based on the ideXlab platform.
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the effects of long term low dose diazepam treatment on the guinea pig Righting Reflex and medial vestibular nucleus neuronal activity
Pharmacology Biochemistry and Behavior, 1995Co-Authors: Mark A Hutchinson, Cynthia L Darlington, Paul F SmithAbstract:Abstract Guinea pigs received a 2 mg/kg IP injection of diazepam, or an equivalent volume of vehicle, daily for 28–60 days. To determine whether tolerance developed to the ataxic effects of diazepam on the Righting Reflex, daily Righting Reflex latency (RRL) measurements were made before and 20, 30, and 40 min following the diazepam or vehicle injection for 28 days. Analyses of the RRLs for individual animals indicated that a significant decrease in RRL over time (indicating tolerance) occurred in only one out of nine animals receiving diazepam and in none of the vehicle animals. Medial vestibular nucleus (MVN) neurons in brain stem slices from animals receiving chronic diazepam treatment had a significantly higher average firing rate than those from vehicle controls. These results suggest that: a) long-term treatment with single 2 mg/kg daily IP injections of diazepam does not result in tolerance to diazepam's ataxic effects on the Righting Reflex in the majority of animals; b) this form of diazepam treatment may, nonetheless, induce a hyperactivity of brain stem MVN neurons that may be consistent with the occurrence of a withdrawal syndrome.
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quantification of the depressive effects of diazepam on the guinea pig Righting Reflex
Pharmacology Biochemistry and Behavior, 1994Co-Authors: Sarah J Scott, Paul F Smith, Cynthia L DarlingtonAbstract:The effects of 5 mg/kg/day diazepam (IP for 21–39 days) on Righting Reflex latency (RRL) and neuronal activity in the medial vestibular nucleus (MVN) were investigated in guinea pigs. Diazepam treatment increased the RRL relative to vehicle-injected controls (p < 0.05, ANOVA); although the average RRL in the diazepam-treated animals did decrease over time, this decrease was not statistically significant and therefore evidence of tolerance was not obtained. MVN slices were removed from diazepam-treated animals and recordings were made from MVN neurons in vitro. The average resting activities for MVN neurons in slices from diazepam-treated animals and uninjected animals from a previous study were not significantly different.
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the tolerometer a fast automated method for the measurement of Righting Reflex latency in chronic drug studies
Journal of Neuroscience Methods, 1993Co-Authors: Barry Dingwall, Bradley Reeve, Paul F Smith, Mark A Hutchinson, Cynthia L DarlingtonAbstract:We describe a fast, automated system for the measurement of Righting Reflex latencies in drug studies. This system, which we call a “tolerometer”, is especially useful for studies of drug tolerance which require a simple measurement of motor behaviour on a daily basis, for long periods of time. The tolerometer consists of a semi-cylindrical platform positioned on a 2 kg load cell, connected to a strain gauge amplifier (Radio Spares Ltd). The output from the amplifier is connected to a MacLab data acquisition system (Analog Digital Instruments), controlled by a Macintosh Classic computer. The MacLab Chart program is used to display, on the Macintosh screen, the load changes which occur during a Righting Reflex; sampling frequencies up to 40 kHz can be used, but we find 20–100 Hz adequate. Using measurement cursors provided by the Chart program, the latency from the point at which an animal is placed on the tolerometer platform in the supine position, until the completion of a Righting Reflex, can be measured accurately and easily.
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simple device for quantifying drug effects on the Righting Reflex
Pharmacology Biochemistry and Behavior, 1992Co-Authors: Bradley Reeve, Barry Dingwall, Cynthia L Darlington, Sarah J Scott, Andrew J Sansom, Paul F SmithAbstract:Abstract A simple, inexpensive device is described that allows quantification of the effects of drugs on the Righting Reflex. This device consists of a modified set of kitchen scales connected to a digital timer. Two moveable Hall effect switches are positioned around the pointer, which registers the weight of the animal on the scales; when the animal is placed on the scales in the supine position, the initiation of a Righting Reflex causes the pointer to cross one of the switches, stopping the digital timer and providing a measure of Righting Reflex latency (RRL). We describe an efficient protocol for using this device that provides quantification of drug effects on the RRL, which can then be subjected to analysis using parametric statistics such as analysis of variance.
Stuart C Clarkprice - One of the best experts on this subject based on the ideXlab platform.
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effects of intracoelomic alfaxalone dexmedetomidine on Righting Reflex in common garter snakes thamnophis sirtalis preliminary data
Veterinary Anaesthesia and Analgesia, 2020Co-Authors: Kelly Chen, Stephanie C J Keating, Danielle Strahlheldreth, Stuart C ClarkpriceAbstract:Abstract Objective To evaluate the effect of dexmedetomidine on alfaxalone immobilization in snakes. Study design Nonblinded, crossover study. Animals A total of eight mature common garter snakes (Thamnophis sirtalis). Methods Snakes were administered each of three treatments intracoelomically: alfaxalone (30 mg kg−1; treatment A), alfaxalone (30 mg kg−1) combined with dexmedetomidine (0.05 mg kg−1; treatment AD0.05); and alfaxalone (30 mg kg−1) combined with dexmedetomidine (0.10 mg kg−1; treatment AD0.10). A minimum of 10 days elapsed between experimental trials. Time to loss of Righting Reflex (LRR) and return of Righting Reflex (RRR) were recorded. Heart rate (HR) was recorded every 5 minutes throughout the period of LRR and averaged for each snake. Time to LRR and RRR, and mean HR in snakes that achieved LRR were reported. Results LRR occurred in eight (100%), five (63%) and three (38%) snakes in treatments A, AD0.05 and AD0.10, respectively. For all treatments, time to LRR ranged 3–20 minutes. Median (range) time to RRR was 39 (30–46) minutes for A, 89 (62–128) minutes for AD0.05 and 77 (30–185) minutes for AD0.10. In animals where Righting Reflex was lost, mean HR was lower in all dexmedetomidine treatments compared with treatment A. Conclusions and clinical relevance In this pilot study, alfaxalone resulted in reliable immobilization, whereas dexmedetomidine and alfaxalone combinations resulted in highly variable durations of immobilization with low HR in immobilized animals. For snakes that achieved LRR, the addition of dexmedetomidine (0.05 mg kg−1) to alfaxalone appeared to extend the period of immobilization compared with alfaxalone alone.
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effect of intracoelomic administration of alfaxalone on the Righting Reflex and tactile stimulus response of common garter snakes thamnophis sirtalis
American Journal of Veterinary Research, 2019Co-Authors: Danielle Strahlheldreth, Stephanie C J Keating, Stuart C Clarkprice, Gabriela C Escalante, Lynelle F Graham, Sathya K Chinnadurai, David J SchaefferAbstract:OBJECTIVE: To determine the intracoelemic (ICe) dose of alfaxalone required to induce loss of Righting Reflex (LRR) in garter snakes (Thamnophis sirtalis) and to evaluate the tactile stimulus respo...
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loss and return of Righting Reflex in american green tree frogs hyla cinerea after topical application of compounded sevoflurane or isoflurane jelly a pilot study
Journal of herpetological medicine and surgery, 2014Co-Authors: Stuart C Clarkprice, David A Coleman, Mark A MitchellAbstract:Abstract The topical application of isoflurane and sevoflurane compounded jellies has been used successfully to anesthetize anurans. Although sevoflurane is a less tissue-soluble anesthetic than isoflurane, it is unknown whether tissue solubility affects anesthesia after topical application. The purpose of this study was to determine time to loss and return of Righting Reflex in eight American green tree frogs, Hyla cinerea, after topical application of compounded isoflurane or sevoflurane jelly. Frogs were placed into a container with either 2 ml of isoflurane or sevoflurane jelly. Containers were intermittently inverted until loss of Righting Reflex was observed. Frogs were then removed, rinsed clean of the jelly, and placed in new containers in dorsal recumbency. Frogs were observed until their Righting Reflex returned. Four frogs initially tested with isoflurane developed skin lesions, and two subsequently died. Accordingly, the isoflurane jelly was discontinued. Frogs exposed to isoflurane lost their...
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effects of sevoflurane anesthesia on Righting Reflex and hemolymph gas analysis variables for chilean rose tarantulas grammostola rosea
American Journal of Veterinary Research, 2014Co-Authors: Trevor T Zachariah, Stuart C Clarkprice, Mark A Mitchell, Megan K Watson, Maureen McmichaelAbstract:Objective—To determine the safety, efficacy, and effects on hemolymph gas analysis variables of sevoflurane anesthesia in Chilean rose tarantulas (Grammostola rosea). Animals—12 subadult Chilean rose tarantulas of unknown sex. Procedures—Spiders were anesthetized in a custom chamber with sevoflurane (5% in oxygen [1.0 L/min]), then allowed to recover in 100% oxygen. Righting Reflex was evaluated every 3 minutes during anesthesia to determine time to anesthetic induction and recovery. Hemolymph samples were collected from an intracardiac location prior to and after induction of anesthesia and evaluated to determine various gas analysis variables. Results—Mean ± SD induction and recovery times were 16 ± 5.91 minutes and 29 ± 21.34 minutes, respectively. Significant differences were detected for Po2, base excess, and glucose and ionized magnesium concentrations between hemolymph samples obtained before anesthesia and those obtained after induction of anesthesia. Conclusions and Clinical Relevance—Results of ...
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evaluation of Righting Reflex in cane toads bufo marinus after topical application of sevoflurane jelly
American Journal of Veterinary Research, 2013Co-Authors: Sabrina M Stone, Stuart C Clarkprice, Jordyn M Boesch, Mark A MitchellAbstract:Results—6 of 8 toads in trial 1 and 8 of 8 toads in trial 2 lost the Righting Reflex. Mean ± SD time to loss of the Reflex was 8.2 ± 1.3 minutes for trial 1 and 8.3 ± 0.9 minutes for trial 2; this difference was not significant. Mean ± SD time to return of the Reflex was 25.6 ± 26.2 minutes for trial 1 and 84.4 ± 47.2 minutes for trial 2; this difference was significant. Chamber sevoflurane concentration did not change significantly, compared with baseline (time 0) concentration, at any time in trial 1; however, there was a significant change in chamber sevoflurane concentration from baseline (time 0) concentration in trial 2. Chamber sevoflurane concentrations were not significantly different between trial 1 and trial 2 at any time. Mean ± SD chamber sevoflurane concentration was 0.46 ± 0.2% for trial 1 and 0.57 ± 0.28% for trial 2. Conclusions and Clinical Relevance—Sevoflurane jelly applied topically at a dose of 37.5 L/g induced a more reliable loss of Righting Reflex and longer recovery time than when applied at a dose of 25 L/g in cane toads. (Am J Vet Res 2013;74:823–827)
Michio Kawahara - One of the best experts on this subject based on the ideXlab platform.
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mk 801 enhances gabaculine induced loss of the Righting Reflex in mice but not immobility
Canadian Journal of Anaesthesia-journal Canadien D Anesthesie, 2007Co-Authors: Masahiro Irifune, Yoshitaka Shimizu, Katsuya Morita, Sohtaro Katayama, Tohru Takarada, Chie Endo, Takashi Takata, Toshihiro Dohi, Tomoaki Sato, Michio KawaharaAbstract:Purpose: γ-Aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) receptors are important targets for anesthetic action at the in vitro cellular level. Gabaculine is a GABA-transaminase inhibitor that increases endogenous GABA in the brain, and enhances GABA activity. We have recently shown that unconsciousness is associated with the enhanced GABA activity due to gabaculine, but that immobility is not. MK-801 is a selective NMDA channel blocker. In this study, we examined behaviourally whether gabaculine in combination with MK-801 could produce these components of the general anesthetic state. We further compared the effect of MK-801 with ketamine, another NMDA channel blocker. Methods: All drugs were administered intraperitoneally to adult male ddY mice. To assess the general anesthetic components, two endpoints were used. One was loss of the Righting Reflex (LORR; as a measure of unconsciousness) and the other was loss of movement in response to tail-clamp stimulation (as a measure of immobility). Results: Large doses of MK-801 alone (10–50 mg·kg –1 ) induced neither LORR nor immobility in response to noxious stimulation. However, even a small dose (0.2 mg·kg –1 ) significantly enhanced gabaculine-induced LORR (P < 0.05), although gabaculine in combination with MK-801 (0.2–10 mg·kg –1 ) produced no immobility. However, gabaculine plus a subanesthetic dose of ketamine (30 mg·kg –1 ), which acts on NMDA, opioid and nicotinic acetylcholine receptors and neuronal Na + channels, suppressed the pain response, but did not achieve a full effect. Ketamine alone dose-dependently produced both LORR and immobility. Conclusion: These findings suggest that gabaculine-induced LORR is modulated by blocking NMDA receptors, but that immobility is not mediated through GABA or NMDA receptors.
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riluzole a glutamate release inhibitor induces loss of Righting Reflex antinociception and immobility in response to noxious stimulation in mice
Anesthesia & Analgesia, 2007Co-Authors: Masahiro Irifune, Nobuhito Kikuchi, Yoshitaka Shimizu, Katsuya Morita, Tohru Takarada, Chie Endo, Toshihiro Dohi, Tomoaki Sato, Takuya Saida, Michio KawaharaAbstract:BACKGROUND: The general anesthetic state comprises behavioral and perceptual components, including amnesia, unconsciousness, analgesia, and immobility. In vitro, glutamatergic excitatory neurons are important targets for anesthetic action at the cellular and microcircuits levels. Riluzole (2-amino-6-[trifluoromethoxy]benzothiazole) is a neuroprotective drug that inhibits glutamate release from nerve terminals in the central nervous system. Here, we examined in vivo the ability of riluzole to produce components of the general anesthetic state through a selective blockade of glutamatergic neurotransmission. METHODS: Riluzole was administered intraperitoneally in adult male ddY mice. To assess the general anesthetic components, three end-points were used: 1) loss of Righting Reflex (LORR; as a measure of unconsciousness), 2) loss of movement in response to noxious stimulation (as a measure of immobility), and 3) loss of nociceptive response (as a measure of analgesia). RESULTS: The intraperitoneal administration of riluzole induced LORR in a dose-dependent fashion with a 50% effective dose value of 27.4 (23.3-32.2; 95% confidence limits) mg/kg. The behavioral and microdialysis studies revealed that time-course changes in impairment and LORR induced by riluzole corresponded with decreased glutamate levels in the mouse brain. This suggests that riluzole-induced LORR (unconsciousness) could result, at least in part, from its ability to decrease brain glutamate concentrations. Riluzole dose-dependently produced not only LORR, but also loss of movement in response to painful stimulation (immobility), and loss of nociceptive response (analgesia) with 50% effective dose values of 43.0 (37.1-49.9), and 10.0 (7.4-13.5) mg/kg, respectively. These three dose-response curves were parallel, suggesting that the behavioral effects of riluzole may be mediated through a common site of action. CONCLUSIONS: These findings suggest that riluzole-induced LORR, immobility, and antinociception appear to be associated with its ability to inhibit glutamatergic neurotransmission in the central nervous system.
Masahiro Irifune - One of the best experts on this subject based on the ideXlab platform.
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selective blockade of n methyl d aspartate channels in combination with dopamine receptor antagonism induces loss of the Righting Reflex in mice but not immobility
Psychopharmacology, 2015Co-Authors: Nobuhito Kikuchi, Masahiro Irifune, Yoshitaka Shimizu, Keita Yoshida, Katsuya Morita, Takashi Kanematsu, Norimitsu Morioka, Yoshihiro Nakata, Norio SakaiAbstract:Rationale The selective N-methyl-d-aspartate (NMDA) channel blocker MK-801 is known to induce no loss of the Righting Reflex (LORR) and to stimulate catecholaminergic (CAergic) neurons in rodents, playing a crucial role in arousal.
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mk 801 enhances gabaculine induced loss of the Righting Reflex in mice but not immobility
Canadian Journal of Anaesthesia-journal Canadien D Anesthesie, 2007Co-Authors: Masahiro Irifune, Yoshitaka Shimizu, Katsuya Morita, Sohtaro Katayama, Tohru Takarada, Chie Endo, Takashi Takata, Toshihiro Dohi, Tomoaki Sato, Michio KawaharaAbstract:Purpose: γ-Aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) receptors are important targets for anesthetic action at the in vitro cellular level. Gabaculine is a GABA-transaminase inhibitor that increases endogenous GABA in the brain, and enhances GABA activity. We have recently shown that unconsciousness is associated with the enhanced GABA activity due to gabaculine, but that immobility is not. MK-801 is a selective NMDA channel blocker. In this study, we examined behaviourally whether gabaculine in combination with MK-801 could produce these components of the general anesthetic state. We further compared the effect of MK-801 with ketamine, another NMDA channel blocker. Methods: All drugs were administered intraperitoneally to adult male ddY mice. To assess the general anesthetic components, two endpoints were used. One was loss of the Righting Reflex (LORR; as a measure of unconsciousness) and the other was loss of movement in response to tail-clamp stimulation (as a measure of immobility). Results: Large doses of MK-801 alone (10–50 mg·kg –1 ) induced neither LORR nor immobility in response to noxious stimulation. However, even a small dose (0.2 mg·kg –1 ) significantly enhanced gabaculine-induced LORR (P < 0.05), although gabaculine in combination with MK-801 (0.2–10 mg·kg –1 ) produced no immobility. However, gabaculine plus a subanesthetic dose of ketamine (30 mg·kg –1 ), which acts on NMDA, opioid and nicotinic acetylcholine receptors and neuronal Na + channels, suppressed the pain response, but did not achieve a full effect. Ketamine alone dose-dependently produced both LORR and immobility. Conclusion: These findings suggest that gabaculine-induced LORR is modulated by blocking NMDA receptors, but that immobility is not mediated through GABA or NMDA receptors.
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riluzole a glutamate release inhibitor induces loss of Righting Reflex antinociception and immobility in response to noxious stimulation in mice
Anesthesia & Analgesia, 2007Co-Authors: Masahiro Irifune, Nobuhito Kikuchi, Yoshitaka Shimizu, Katsuya Morita, Tohru Takarada, Chie Endo, Toshihiro Dohi, Tomoaki Sato, Takuya Saida, Michio KawaharaAbstract:BACKGROUND: The general anesthetic state comprises behavioral and perceptual components, including amnesia, unconsciousness, analgesia, and immobility. In vitro, glutamatergic excitatory neurons are important targets for anesthetic action at the cellular and microcircuits levels. Riluzole (2-amino-6-[trifluoromethoxy]benzothiazole) is a neuroprotective drug that inhibits glutamate release from nerve terminals in the central nervous system. Here, we examined in vivo the ability of riluzole to produce components of the general anesthetic state through a selective blockade of glutamatergic neurotransmission. METHODS: Riluzole was administered intraperitoneally in adult male ddY mice. To assess the general anesthetic components, three end-points were used: 1) loss of Righting Reflex (LORR; as a measure of unconsciousness), 2) loss of movement in response to noxious stimulation (as a measure of immobility), and 3) loss of nociceptive response (as a measure of analgesia). RESULTS: The intraperitoneal administration of riluzole induced LORR in a dose-dependent fashion with a 50% effective dose value of 27.4 (23.3-32.2; 95% confidence limits) mg/kg. The behavioral and microdialysis studies revealed that time-course changes in impairment and LORR induced by riluzole corresponded with decreased glutamate levels in the mouse brain. This suggests that riluzole-induced LORR (unconsciousness) could result, at least in part, from its ability to decrease brain glutamate concentrations. Riluzole dose-dependently produced not only LORR, but also loss of movement in response to painful stimulation (immobility), and loss of nociceptive response (analgesia) with 50% effective dose values of 43.0 (37.1-49.9), and 10.0 (7.4-13.5) mg/kg, respectively. These three dose-response curves were parallel, suggesting that the behavioral effects of riluzole may be mediated through a common site of action. CONCLUSIONS: These findings suggest that riluzole-induced LORR, immobility, and antinociception appear to be associated with its ability to inhibit glutamatergic neurotransmission in the central nervous system.
