Intrathecal neurokinin-1 receptor antagonist reduces isoflurane MAC in rats

Purpose

To study the effects of intrathecal administration of a neurokinin-l(NK-l) receptor antagonist (CP96.345) on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in anaesthetized rats, and on the locomotive activity of conscious rats.

Methods

Wistar rats (n = 36) were fitted with indwelling intrathecal catheters, and the MAC of isoflurane was determined following the intrathecal administration of saline (control group) or the NK-1 receptor antagonist CP96.345 (CP) at 1, 10 and 100 μg. Subsequently a reversal dose of intrathecal Substance P (SP) at 1. 10 and 100 μg was administered and MAC isoflurane was redetermined. Conscious rats (n = 35) were also examined for the presence of locomotor dysfunction following intrathecal administration of CP and SP Animals were randomly assigned to each treatment group and the investigators were blinded.

Results

CP at 10 and I00 μg reduced MAC isoflurane by 9.9% and 15.3%, respectively (P < 0.05). Intrathecal administration of SP reversed the decreases in MAC by CP; however, locomotive activity was not changed.

Conclusion

These results suggest that the NK-1 receptor plays an important role in determining the MAC of isoflurane by inhibition of pain transmission in the spinal cord.     

Cardiopulmonary bypass reduces the minimum alveolar concentration for isoflurane

OBJECTIVE: The purpose of this investigation was to determine the influence of cardiopulmonary bypass (CPB) on the minimum alveolar concentration (MAC) of isoflurane in a rat model of CPB. DESIGN: Prospective. SETTING: University research laboratory. PARTICIPANTS: Sprague-Dawley rats. INTERVENTIONS: Using tail-clamp methodology, the pre- and post-CPB MAC for isoflurane was studied. METHODS AND MAIN RESULTS: Rats were anesthetized with isoflurane, intubated, ventilated, and surgically prepared for CPB, after which they were randomized to either Sham-operated or CPB groups. The CPB group (n = 10) underwent 90 minutes of normothermic nonpulsatile CPB. The Sham group (n = 13) were cannulated but did not undergo CPB. Pre- and post-CPB MAC determinations were compared within groups using a paired Student t test. The CPB group had a pre-CPB baseline isoflurane MAC of 1.09% +/- 0.11% versus 1.09% +/- 0.08% in the Sham group (p = 0.90). Twenty minutes after CPB, the CPB group exhibited a decrease in MAC to 0.98% +/- 0.14% (p = 0.0026, compared with baseline). The MAC in the Sham group was unchanged (p = 0.5852, compared with baseline). Two hours after CPB, the MAC in the CPB group remained lower compared with baseline at 0.99% +/- 0.14% (p = 0.0032). CONCLUSIONS: CPB resulted in a small (10%) but significant reduction in the MAC for isoflurane. The mechanism behind this reduction in MAC is not clear but may be related to CPB-induced cerebral injury.     

Intrathecal morphine reduces the minimum alveolar concentration of halothane in humans

The authors hypothesized that the analgesia provided by intraspinal opiates would decrease anesthetic requirement. To test this hypothesis, 20 women undergoing major gynecologic surgery were divided randomly into two groups. One group received 0.75 mg morphine sulfate intrathecally, and the other, the same dose intramuscularly (control), prior to the induction of anesthesia with halothane. MAC for halothane was 0.81% in the control group and 0.46% in the intrathecal morphine group (P = 0.024). The reduction in anesthetic requirement due to intrathecal morphine is greater than that produced by low to moderate doses of systemically administered opiates.     

Intrathecal co-administration of NMDA antagonist and NK-1 antagonist reduces MAC of isoflurane in rats

BACKGROUND: Intravenous administration of N-methyl-D-aspartate (NMDA) receptor antagonists and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists reportedly reduce the minimum alveolar anaesthetic concentration (MAC) for inhalation anaesthetics. If pain perception can be prevented by the intrathecal administration of antinociceptive receptor antagonists, these agents may reduce the requirements for inhalation anaesthetics. We studied the effect of intrathecal administration of an AMPA/kainate receptor antagonist, a metabotropic glutamate (mGlu) receptor antagonist and co-administration of NMDA and a neurokinin-1(NK-1) receptor antagonist drugs at low doses on the MAC. METHODS: After Wistar rats (n=36) were fitted with indwelling intrathecal catheters, the MAC of isoflurane was determined following intrathecal administration of a non-NMDA receptor antagonist (CNQX) at 10 microg, a mGlu receptor antagonist (AP3) at 10 microg, or a combination of NMDA receptor antagonist (APV) at 0.01 microg to 1 microg with NK-1 receptor antagonist (CP96345, CP) at 0.1 microg to 10 microg. Subsequently, a reversal dose of intrathecal NMDA with substance P (SP) was administered, and the MAC of isoflurane was redetermined. Conscious rats (n=15) were also examined for the presence of locomotor dysfunction following the intrathecal co-administration of APV and CP. RESULTS: Neither CNQX nor AP3 reduced the MAC of isoflurane. APV at 0.01 microg plus CP at 1 microg, as well as APV at 0.1 microg plus CP at 10 microg, reduced the MAC of isoflurane, with respective reductions of 7.6% and 14%; (P<0.05). Co-administration of NMDA plus SP reversed the decrease in the MAC of isoflurane. Locomotive activity was not changed. CONCLUSIONS: The NMDA receptor and the NK-1 receptor are important determinants of the MAC of isoflurane, exerting this influence by inhibition of pain transmission in the spinal cord, while mGlu and AMPA receptors have no effect on the MAC of isoflurane.     

Inhibition of glutamate transporters increases the minimum alveolar concentration for isoflurane in rats

Background. Glutamate transporters [also named excitatory aminoacid transporters (EAATs)] bind and take up extracellular glutamate,a major excitatory neurotransmitter, and can regulate glutamatergicneurotransmission in synapses. As anaesthesia is proposed tobe induced by enhancing inhibitory neurotransmission, inhibitingexcitatory neurotransmission, or both we hypothesize that inhibitionof EAAT activity can increase the anaesthetic requirement. Methods. The minimum alveolar concentration (MAC, the anaestheticconcentration required to suppress movement in response to noxiousstimulation in 50% of subjects) for isoflurane was determinedin adult male Sprague–Dawley rats after intrathecal administrationof EAAT inhibitors. Results. Application of DL-threo-ß-benzyloxyaspartate,a selective EAAT inhibitor, dose- and time-dependently increasedthe MAC for isoflurane. The MAC was 109 (1)% and 116 (4)% ofthe baseline, respectively, for 0.2 and 0.4 µmol of DL-threo-ß-benzyloxyaspartate15 min after the injection of the drug (n=5, P<0.05 comparedwith the baseline MAC). Intrathecal injection of dihydrokainate,a selective inhibitor of EAAT type 2, also increased the MACfor isoflurane. Conclusions. These results suggest that EAAT in the spinal cordcan regulate the requirement of isoflurane to induce immobility.EAAT2 may be involved in this effect.     

Flumazenil decreases the minimum alveolar concentration isoflurane in dogs

Flumazenil is a potent-specific benzodiazepine receptor antagonist that has been shown to reverse CNS depressant effects mediated by benzodiazepine agonists. These agonists are known to affect the interaction of gamma aminobutyric acid (GABA) with its receptor. Because the action of volatile anesthetic agents may be mediated by GABA, the authors determined the MAC of isoflurane in 16 dogs before and after one of three doses of intravenous flumazenil (0.15, 0.3, and 0.45 mg/kg) or the drug vehicle. The flumazenil produced a reduction in MAC from 1.39 +/- 0.15% (mean +/- SD) to 1.23 +/- 0.11% after 0.15 mg/kg (P less than 0.05), from 1.50 +/- 0.35% to 1.08 +/- 0.20% after 0.3 mg/kg (P less than 0.01), and from 1.45 +/- 0.14% to 1.09 +/- 0.08% after 0.45 mg/kg (P less than 0.01). Administration of drug vehicle produced no change in MAC. This reduction in isoflurane requirement by flumazenil may be due to its benzodiazepine receptor agonist action or its analgesic effect.     

The effects of intravenous lidocaine administration on the minimum alveolar concentration of isoflurane in cats

Lidocaine decreases the minimum alveolar concentration (MAC) of inhaled anesthetics and has been used clinically to reduce the requirements for other anesthetic drugs. In this study we examined the effects of lidocaine on isoflurane MAC in cats. Six cats were studied. In Experiment 1, the MAC of isoflurane was determined. An IV bolus of lidocaine 2 mg/kg was then administrated and venous plasma lidocaine concentrations were measured to determine pharmacokinetic values. In Experiment 2, lidocaine was administered to achieve target plasma concentrations between 1 and 11 microg/mL and the MAC of isoflurane was determined at each lidocaine plasma concentration. Actual lidocaine plasma concentrations were 1.06 +/- 0.12, 2.83 +/- 0.39, 4.93 +/- 0.64, 6.86 +/- 0.97, 8.86 +/- 2.10, and 9.84 +/- 1.34 microg/mL for the target concentrations of 1, 3, 5, 7, 9, and 11 microg/mL, respectively. The MAC of isoflurane in this study was 2.21% +/- 0.17%, 2.14% +/- 0.14%, 1.88% +/- 0.18%, 1.66% +/- 0.16%, 1.47% +/- 0.13%, 1.33% +/- 0.23%, and 1.06% +/- 0.19% at lidocaine target plasma concentrations of 0, 1, 3, 5, 7, 9, and 11 microg/mL, respectively. Lidocaine, at target plasma concentrations of 1, 3, 5, 7, 9, and 11 microg/mL, linearly decreased isoflurane MAC by -6% to 6%, 7% to 28%, 19% to 35%, 28% to 45%, 29% to 53%, and 44% to 59%, respectively. We conclude that lidocaine decreases the MAC of isoflurane.     

Nimodipine decreases the minimum alveolar concentration of isoflurane in dogs

Nimodipine is a calcium antagonist that binds with high affinity to neuronal membranes. It is a potent cerebrovasodilator and has been demonstrated also to affect neurotransmitter synthesis and release. Because patients undergoing surgery for intracranial aneurysms are frequently receiving nimodipine, the authors determined the MAC of isoflurane in six dogs before and during three infusion doses of nimodipine (0.5, 1.0 and 2.0 micrograms.kg-1.min-1). MAC was also determined in five dogs before and during infusion of the drug vehicle (10 microliters.kg-1.min-1). Nimodipine produced a reduction in MAC from 1.47 +/- 0.33% to 1.19 +/- 0.18, 1.15 +/- 0.18 and 1.15 +/- 0.09% during infusions of nimodipine 0.5, 1.0 and 2.0 micrograms.kg-1.min-1, respectively (P less than 0.05). Infusion of drug vehicle alone produced no change in MAC (1.39 +/- 0.15%). This reduction in anaesthetic requirement by nimodipine may be due to its effect on neurotransmission. Adjustments in anaesthetic dosage may be necessary in patients receiving nimodipine.     

Effects of tramadol on minimum alveolar concentration (MAC) of isoflurane in rats

It has been suggested previously that tramadol increases central nervous system activity and 'lightens' anaesthesia with volatile agents. We assessed the effects of tramadol on the minimum alveolar concentration (MAC) of isoflurane in 56 Wistar rats, instrumented chronically with an arterial and central venous catheter. The MAC of isoflurane was determined using the tail clamp method under three conditions: (1) after injection of saline (control); (2) after administration of tramadol 10 mg kg-1 i.v.; and (3) after administration of morphine 1 mg kg-1 i.v. The studies were repeated after treatment with the antagonists naloxone or yohimbine. Tramadol and morphine both reduced the MAC of isoflurane from mean 1.38 (SEM 0.05)% to 1.22 (0.06)% and 1.17 (0.06)%, respectively (P < 0.05). Concomitant administration of yohimbine did not abolish this reduction in MAC. In contrast, after pretreatment with naloxone, tramadol (1.47 (0.04)%) or morphine (1.38 (0.07)%) did not cause a reduction in the MAC of isoflurane compared with controls (1.39 (0.06)%). We conclude that tramadol and morphine reduced the MAC of isoflurane to a small but significant extent. For both drugs, this effect was related to their action at opioid receptors.      

Halothane and isoflurane have additive minimum alveolar concentration (MAC) effects in rats

Studies suggest that at concentrations surrounding MAC (the minimum alveolar concentration suppressing movement in 50% of subjects in response to noxious stimulation), halothane depresses dorsal horn neurons more than does isoflurane. Similarly, these anesthetics may differ in their effects on various receptors and ion channels that might be anesthetic targets. Both findings suggest that these anesthetics may have effects on movement in response to noxious stimulation that would differ from additivity, possibly producing synergism or even antagonism. We tested this possibility in 20 rats. MAC values for halothane and (separately) for isoflurane were determined in duplicate before and after testing the combination (also in duplicate; six determinations of MAC for each rat). The sum of the isoflurane and halothane MAC fractions for individual rats that produced immobility equaled 1.037 +/- 0.082 and did not differ significantly from a value of 1.00. That is, the combination of halothane and isoflurane produced immobility in response to tail clamp at concentrations consistent with simple additivity of the effects of the anesthetics. These results suggest that the immobility produced by inhaled anesthetics need not result from their capacity to suppress transmission through dorsal horn neurons. IMPLICATIONS: Despite differences in their capacities to inhibit spinal dorsal horn cells, isoflurane and halothane are additive in their ability to suppress movement in response to a noxious stimulus.     

The effects of i.v. fentanyl administration on the minimum alveolar concentration of isoflurane in horses

Background. Fentanyl decreases the minimum alveolar concentration(MAC) of inhaled anaesthetics and has been used clinically toreduce the requirements of other anaesthetic drugs in humansand small animals. We hypothesized that i.v. fentanyl woulddecrease the MAC of isoflurane in horses in a dose-dependentmanner. Methods. Following determination of baseline MAC of isoflurane,fentanyl was administered i.v. to target plasma concentrationsof 1, 8 and 16 ng ml^–1. Each horse was randomly assignedtwo of three target concentrations administered in ascendingorder. Loading and infusion doses for each horse were determinedfrom previously derived individual pharmacokinetic values. IsofluraneMAC determination began 45 min after fentanyl administrationat each target fentanyl concentration. Venous blood was collectedat fixed intervals during the infusion for measurement of plasmafentanyl concentrations. Results. Mean actual fentanyl plasma concentrations were 0 (baseline),and 0.72 (SD 0.26), 8.43 (3.22), and 13.31 (6.66) ng ml^–1for the target concentrations of 1, 8 and 16 ng ml^–1,respectively. The corresponding isoflurane MAC values were abaseline of 1.57 (0.23), and 1.51 (0.24), 1.41 (0.23) and 1.37(0.09)%, respectively. The fentanyl concentrations of 0.72 and8.43 ng ml^–1 did not significantly alter the MAC of isoflurane,but an 18 (7)% ISO-MAC reduction was observed at the 13.31 ngml^–1 concentration. Conclusions. These results cautiously encourage further studyof fentanyl as an opioid anaesthetic adjunct to inhalant anaesthesiain horses.     

Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold in rats

Canadian Journal of Anesthesia/Journal canadien d'anesthésie - The purpose of this study was to examine the anaesthetic requirement of intrathecal midazolam in a dose-response fashion in...     

Insulin decreases isoflurane minimum alveolar anesthetic concentration in rats independently of an effect on the spinal cord

The observation that insulin supplies an element of analgesia suggests that insulin administration might decrease the concentration of inhaled anesthetic required to produce MAC (the minimum alveolar anesthetic concentration required to eliminate movement in response to noxious stimulation in 50% of subjects). We hypothesized that insulin decreases MAC by directly affecting the nervous system, by decreasing blood glucose, or both. To test these hypotheses, we infused increasing doses of insulin either intrathecally or IV in rats anesthetized with isoflurane and determined the resulting MAC change (assessing forelimb and hindlimb movement separately). Infusion of insulin produced a dose-related decrease in MAC that did not differ among groups. That is, the IV and intrathecal infusions caused similar decreases in MAC at a given infusion rate. Blood glucose concentrations were larger in the rats given insulin with 5% dextrose. However, the percentage change in MAC determined from forelimb versus hindlimb movement did not differ. For a given insulin infusion rate, MAC changes and glucose levels did not correlate with each other, except, possibly, for the most rapid infusion rate, for which smaller glucose concentrations were associated with a marginally larger decrease in MAC. Intrathecal infusions of insulin did not produce spinal cord injury. In summary, we found that insulin decreases isoflurane MAC in a dose-related manner independently of its effects on the blood concentration of glucose. The sites at which insulin acts to decrease MAC appear to be supraspinal rather than spinal. The effect may be due to a capacity of insulin to produce analgesia through an action on one or more neurotransmitter receptors. IMPLICATIONS: Intrathecal and IV insulin administration equally decrease isoflurane MAC in rats, regardless of the concentration of blood sugar. These findings indicate that although insulin decreases MAC, the decrease is not mediated by actions on the spinal cord.     

Comparison of minimum alveolar concentration between intravenous isoflurane lipid emulsion and inhaled isoflurane in dogs

BACKGROUND: As in inhaled isoflurane anesthesia, when isoflurane lipid emulsion (ILE; 8%, vol/vol) is intravenously administered, the primary elimination route is through the lungs. This study was designed to determine the minimum alveolar concentration (MAC) and the time course of washout of isoflurane for intravenously infused ILE by monitoring end-tidal isoflurane concentration. METHODS: Twelve healthy adult mongrel dogs were assigned randomly to an intravenous anesthesia group with 8% ILE or to an inhalation anesthesia group with isoflurane vapor. An up-and-down method and stimulation of tail clamping were used to determine MAC of 8% ILE by intravenous injection in the intravenous anesthesia group and MAC by the inhaled approach in the inhalation anesthesia group, respectively. Isoflurane concentration and partial pressure in end-tidal gas, femoral arterial blood, and jugular venous blood were measured simultaneously just before each tail clamping and during washout. RESULTS: The induction time in the intravenous anesthesia group (105 +/- 24 s) was shorter than that in the inhalation anesthesia group (378 +/- 102 s; P < 0.01). MAC of 8% ILE by intravenous injection (1.12 +/- 0.18%) was significantly less than MAC by the inhaled approach (1.38 +/- 0.16%; P < 0.05). No significant difference was found between the two groups in the time course of washout of isoflurane. CONCLUSION: The MAC of intravenous anesthesia with 8% ILE was less than that of inhalation anesthesia with isoflurane vapor in dogs.     

Temporal summation governs part of the minimum alveolar concentration of isoflurane anesthesia

BACKGROUND: General anesthesia may delay the onset of movement in response to noxious stimulation. The authors hypothesized that the production of immobility could involve depression of time-related processes involved in the generation of movement. METHODS: The delays (latencies) between onset of tail clamp (n = 16) or 50-Hz continuous electrical stimulation (n = 8) and movement were measured in rats equilibrated at 0.1-0.2% increasing steps of isoflurane. In other rats (n = 8), the isoflurane concentrations just permitting and preventing movement (crossover concentrations) in response to trains of 0.5-ms 50-V square-wave pulses of interstimulus intervals of 10, 3, 1, 0.3, or 0.1 s during the step increases were measured. These measures were again made during administration of intravenous MK801, an N-methyl-D-aspartate receptor antagonist that can block temporal summation (n = 6). Temporal summation refers to the cumulative effect of repeated stimuli. Crossover concentrations to 10- and 0.1-s interstimulus interval pulses ranging in voltage from 0.25-50 V were also measured (n = 4). RESULTS: The increase in concentrations from 0.6 to nearly 1.0 minimum alveolar concentration progressively increased latency from less than 1 s to 58 s. Shortening the interstimulus interval (50 V) pulses from 10 to 0.1 s progressively increased crossover concentrations from 0.6 to 1.0 minimum alveolar concentration. In contrast, during MK801 administration shortening interstimulus intervals did not change crossover concentrations, producing a flat response to change in the interstimulus interval. Increasing the voltage of interstimulus interval pulses increased the crossover concentrations but did not change the response to change in interstimulus intervals for pulses greater than 1 V. CONCLUSIONS: Increasing the duration or frequency (interstimulus interval) of stimulation increases the concentration of isoflurane required to suppress movement by a 0.4 minimum alveolar concentration MK801 blocks this effect, a finding consistent with temporal summation (which requires intact N-methyl-D-aspartate receptor activity) at concentrations of up to 1 minimum alveolar concentration isoflurane.     

犬静脉注射乳化异氟醚最低肺泡有效浓度的研究

目的测定犬静脉注射乳化异氟醚的最低肺泡有效浓度(MAC静脉),并与吸入异氟醚麻醉时的最低肺泡有效浓度(MAC吸入)进行比较。方法将40只杂种犬平均分成静脉和吸入麻醉两组。应用序贯法和自身交叉法同时测定犬的MAC值。结果静脉组序贯法所测得的MAC静脉(0.94±0.10)%,与自身交叉法所测得的前6个交叉点的MAC静脉(0.89±0.14)%或全部交叉点的MAC静脉(0.93±0.13)%之间差异均无显著意义(P>0.05)。吸入组序贯法所测得的MAC吸入(1.29±0.10)%,与自身交叉法所测得的前6个交叉点的MAC吸入(1.24±0.06)%或全部交叉点的MAC吸入(1.33±0.09)%之间差异亦无显著意义(P>0.05)。但两组间比较MAC静脉均小于MAC吸入,差异有显著意义(P<0.05)。结论乳化异氟醚静脉麻醉时的MAC静脉明显小于吸入异氟醚麻醉时的MAC吸入,序贯法和自身交叉法对MAC的测定结果无明显影响。     

硬膜外利多卡因对异氟醚和地氟醚MAC的影响

目的 本研究以BIS>50作为指标来确定异氟醚和地氟醚的ED50值(MACBIS50),观察硬膜外利多卡因对异氟醚和地氟醚达到满意麻醉深度时用药量的影响。方法 48例患者随机分为两组:异氟醚组和地氟醚组,每组又随机分全麻复合硬膜外组和单纯全麻组(每组12例)。患者术前阿托品肌肉注射,全麻复合硬膜外组给予1.6％利多卡因10ml。全麻诱导采用咪达唑仑、芬太尼、异丙酚和维库溴铵,诱导插管后吸入异氟醚和地氟醚,待呼气末浓度(ET％)达到预定值并且稳定10 min后,记录相应的BIS值。采用上下波动法分别计算异氟醚和地氟醚MACBIS50,BIS值和呼气末浓度进行直线回归分析。结果MACBIS50全麻复合硬膜外组(异氟醚组0.77％、地氟醚组3.87％)和单纯全麻组(异氟醚组1.16％、地氟醚组5.18％)比较显著降低(P<0.01)。四组BIS和ET％均呈直线相关。结论硬膜外利多卡因可显著降低异氟醚(34％)和地氟醚(53％)维持足够麻醉深度的呼气末浓度,并保持BIS值和呼气末浓度的直线相关性。     

Effect of the deficiency of spinal PSD-95/SAP90 on the minimum alveolar anesthetic concentration of isoflurane in rats

BACKGROUND: Spinal N-methyl-D-aspartate (NMDA) receptor activation has been demonstrated to play an important role in the processing of spinal nociceptive information and in the determination of the minimum alveolar anesthetic concentration (MAC) of inhalational anesthetics. Postsynaptic density-95 (PSD-95)/synapse-associated protein-90 (SAP90), a molecular scaffolding protein that binds and clusters the NMDA receptor perferentially at synapses, was implicated in NMDA-induced thermal hyperalgesia. The current study investigated the possible involvement of PSD-95/SAP9O in determining MAC for isoflurane anesthesia. METHODS: Sprague-Dawley rats were pretreated intrathecally with PSD-95/SAP90 antisense oligodeoxyribonucleotide (ODN), sense ODN, missense ODN, or saline every 24 h for 4 days. After initial baseline determination of the MAC, NMDA or saline was injected intrathecally. Ten minutes later, MAC measurement was repeated. The rats also were evaluated for the presence of locomotor dysfunction by intrathecal administration of NMDA or saline in the saline- and ODN-treated rats. RESULTS: In the groups treated with antisense ODNs, but not in those treated with sense or missense ODNs, there was a significant decrease in isoflurane MAC that was not accompanied by marked changes in either blood pressure or heart rate. In the saline-treated group, intrathecal NMDA caused an increase in isoflurane MAC. In contrast, in the antisense ODN-treated group, intrathecal NMDA did not produce a significant change in isoflurane MAC. An NMDA-induced increase in blood pressure but not heart rate was found in both saline- and antisense ODN-treated groups. Locomotor activity was not changed in any of the treated animals. CONCLUSION: The results indicate not only a significant decrease in MAC for isoflurane but also an attenuation in the NMDA-induced increase in isoflurane MAC in the PSD-95/SAP90 antisense-treated animals, which suggests that PSD-95/SAP90 may mediate the role of the NMDA receptor in determining the MAC of inhalational anesthetics.