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PubMed1993

Occupation of low-affinity cholecystokinin (CCK) receptors by CCK activates signal transduction and stimulates amylase secretion in pancreatic acinar cells.

Based on the effects of monensin on binding of 125I-CCK-8 and its lack of effect on CCK-8-stimulated amylase secretion we previously proposed that pancreatic acinar cells possess three classes of CCK receptors: high-affinity receptors, low-affinity receptors and very low-affinity receptors [1]. In the present study we treated pancreatic acini with carbachol to induce a complete loss of high-affinity CCK receptors and then examined the action of CCK-8 on inositol trisphosphate IP3(1,4,5), cytosolic calcium and amylase secretion in an effort to confirm and extend our previous hypothesis. We found that first incubating pancreatic acini with 10 mM carbachol decreased binding of 125I-CCK-8 measured during a second incubation by causing a complete loss of high-affinity CCK receptors with no change in the low-affinity CCK receptors. Carbachol treatment of acini, however, did not alter the action of CCK-8 on IP3(1,4,5), cytosolic calcium or amylase secretion or the action of CCK-JMV-180 on amylase secretion or on the supramaximal inhibition of amylase secretion caused by CCK-8. The present findings support our previous hypothesis that pancreatic acinar cells possess three classes of CCK receptors and suggest that high-affinity CCK receptors do not mediate the action of CCK-8 on enzyme secretion, that low-affinity CCK receptors may mediate the action of CCK on cytosolic calcium that does not involve IP3(1,4,5) and produce the upstroke of the dose-response curve for CCK-8-stimulated amylase secretion and that very low-affinity CCK receptors mediate the actions of CCK on IP3(1,4,5) and cytosolic calcium and produce the downstroke of the dose-response curve for CCK-8-stimulated amylase secretion. Moreover, CCK-JMV-180 is a full agonist for stimulating amylase secretion by acting at low-affinity CCK receptors and is an antagonist at very low-affinity CCK receptors.

Amylases↗
PubMed1988

Carbon tetrachloride hepatotoxicity in endotoxin tolerant and polymyxin B-treated rats.

Gut-derived endotoxin has been implicated in the hepatotoxic effects of CCl4. The present study has investigated whether two procedures known to block LPS effects would alter the action of CCl4 to decrease hepatic cytochrome P-450 and microsomal drug-metabolizing activity. Administration of polymyxin B or induction of LPS tolerance were shown to attenuate the effect of CCl4 administration to increase SGOT and SGPT levels, signs of hepatic damage. Polymyxin B administration but not LPS tolerance caused a slight decrease in cytochrome P-450. In pretreated animals given CCl4, only those which had received polymyxin B showed a reduced effect of CCl4 to alter cytochrome P-450 level and activity. However, the apparent protective effect was of the same magnitude as the loss of cytochrome P-450 caused by polymyxin B itself. These results suggest that the ability of polymyxin B to ablate the CCl4 loss of P-450 might be due to a reduced metabolic activation of CCl4 by P-450 and not due to any anti-LPS activity. The results suggest that gut-derived LPS does not participate in the effect of CCl4 decreasing cytochrome P-450-mediated reactions. However, participation of LPS in other hepatotoxic effects of CCl4 is not excluded.

Alanine Transaminase↗
PubMed1993

Simultaneous measurement of opiate-induced histamine release in the periaqueductal gray and opiate antinociception: an in vivo microdialysis study.

Histamine release and the subsequent activation of H2 receptors in the periaqueductal gray (PAG) are thought to be important components of morphine antinociception. In vivo microdialysis and antinociceptive testing were simultaneously applied in rats to characterize the effects of morphine on PAG histamine release and determine the relationship between histamine release and antinociception. In the absence of nociceptive (tail pinch) testing, morphine (12.8 mg/kg) induced a delayed, long-lasting release of histamine in the PAG. This effect of morphine was abolished by the opiate antagonist naltrexone (1 mg/kg) but was not mimicked by the mu-preferring agonist fentanyl (0.3 mg/kg), suggesting that activation of an opiate receptor other than, or in addition to, the mu receptor is necessary. In contrast to the findings with fentanyl in untested animals, fentanyl combined with nociceptive testing increased histamine release, even though testing alone had no such effect. Unexpectedly, tail pinch testing inhibited morphine-induced histamine release. These results show that the test procedure alters the action of opiates on histamine release, an effect likely to be the result of the stress of repeated tail pinch testing. Therefore, although histamine release may not be obligatory for all types of opiate antinociception, histamine in the PAG may function as a mediator of stress-induced potentiation of opiate antinociception. Even though the microdialysis technique has been acclaimed for its ability to assess neurochemical and behavioral characteristics simultaneously, the introduction of nociceptive testing clearly can alter the neurochemical systems under study.

Analgesia↗
PubMed1988

The effect of pentylenetetrazol on the metacerebral neuron of Helix pomatia.

The effects of Pentylenetetrazol (PTZ) on the metacerebral giant cell (MCC) of the snail, Helix pomatia were studied. Actions on membrane resistance, time constant, resting and action potentials, outward and inward ionic currents were examined. Superfusion with PTZ in concentrations of 25 to 50 mmol/l, induced a gradually evolving convulsive state, which could be studied by intracellular recording from the MCCs. In the pre-convulsive state an acceleration of the spontaneous activity developed and was followed by paroxysmal depolarization shifts (PDSs), in the convulsive phase. PTZ prolonged the membrane time constant by about 10 percent, but this could not be traced back to alterations in membrane resistance or capacity. The resting membrane potential was not significantly altered; the action potentials were prolonged by slowing down of both the rising and decaying phases. The outward potassium currents were repressed by PTZ in a voltage dependent manner. The decrease of the IA current became more pronounced at increasingly positive command pulses, while IK was relieved from depression especially at longer pulse durations. Inward currents were isolated with the aid of suppression of outward currents by 50 mmol/l TEA. Under these conditions sodium currents, measured in calcium deficient Ringer solution were moderately depressed, while the calcium currents, examined during sodium-free superfusion, were mildly enhanced by PTZ. It is concluded that PTZ effects on ionic conductances, on membrane parameters, on the resting potential and ionic currents explain only modifications of spike potentials occurring in the convulsive state and do not account for the PDS, the central phenomenon of the convulsive electrographic activity, at least in this thoroughly examined type of neuron.

Action Potentials↗
PubMed1980

Effect of local anaesthetics (mesocain) on membrane properties of cat papillary muscle.

In 28 experiments on cat papillary muscles the effect of mesocain (generically related to lidocaine) was studied on transmembrane currents (rapid inward INa, slow inward Isi, outward Io), on the configuration and (dV/dt)max of the action potential, on the refractory period and on isometric tension. The experiments were performed using either voltage clamp method (double sucrose gap) or microelectrode technique. All three transmembrane currents are inhibited by mesocain in a dose-dependent manner. The effect becomes measurable at 10(-6) mol/1 on INa, at 10(-5) mol/1 on Isi and at 5 X 10(-5) mol/1 on Il. INa is blocked at 10(-3) mol/1 concentration. These changes correlate with the measured alterations of action potentials: i.e. a decreased (dV/dt) max and overshoot, lower voltage and shortening of the plateau phase, slower rate of late repolarizaion. The negative inotropic effect appeared with the same treshold concentration as Isi; at higher concentrations, however, this effect was relatively much greater. The recovery of excitability measured by the interval-dependence of (dV/dt) max was prolonged 5 times on the average by mesocain at 10(-4) mol/1 and the effective refractory period was delayed beyond complete repolarization. It is concluded that the main effect of mesocain also involves a delayed kinetics of recovery from inactivation of the Na carrying system.

Action Potentials↗
PubMed1989

Influence of proximal axonal swellings on rhythmic motoneuron firing.

Previous studies of electrophysiological function of motoneurons (MNs) in animals with beta, beta'-iminodipropionitrile (IDPN) neuropathy revealed alterations in action potential discharge indicative of enhanced MN excitability. These changes, particularly manifested in increased numbers of delayed depolarizations and repetitive firing upon single stimulation, are strikingly similar to those observed in axotomized MNs. The present study extends the parallels between axotomized and neuropathic conditions by assessing rhythmic firing responses of MNs to direct current injection in cats treated with IDPN (50 mg/kg/week for 5 weeks). Changes in excitability and frequency-current relationships were studied on Day 35 of IDPN intoxication and compared to those reported for axotomized (chromatolytic) MNs. In treated animals, lumbar MNs had increased thresholds for sustained discharge, tended to achieve higher maximum discharge frequencies, and adapted less to continuous current injection. In untreated cats 74% of MNs exhibited firing in both primary and secondary ranges, whereas only 39% of those in treated animals made the transition to secondary range firing. Most fired monotonically in the primary range with unchanged slope of the frequency-current relationships. When achieved, secondary range slopes were one-third of normal. MN afterhyperpolarization peak amplitude, duration, and conductance were reduced while input resistance was increased. The findings are discussed in terms of altered MN and dendritic excitability induced by the neuropathy, and similarities to electrophysiological changes in axotomized MNs.

Action Potentials↗
PubMed1992

Activation of C fibers by metabolic perturbations associated with tourniquet ischemia.

Peripheral A-delta and C fibers are activated during the production of ischemic or tourniquet pain; however, individual metabolic or molecular factors responsible for neural activation are not known. To elucidate these mechanisms the in vitro corneal nerve preparation was used. Electrophysiologic effects of individual metabolic perturbations associated with ischemia (hypoxia, hypoglycemia, lactic acid, and decreased pH) were investigated on A-delta and C fiber nociceptors. Increased tonic action potential activity occurred in C fibers but not in A-delta fibers after ischemia. The conduction velocity of C fibers was 0.85 +/- 0.2 m/s (mean +/- SD). Under control conditions (n = 43) there was very little fluctuation in the baseline action potential frequency (+/- 3.2%). Hypoxia (n = 12) resulted in a 213 +/- 3.4% (mean +/- SD) increase in C fiber action potential frequency relative to control (P less than 0.001, ANOVA). L-glucose substitution for D-glucose (n = 8) increased C fiber discharge frequency by 653 +/- 28% relative to control (P less than 0.001) as did the combination of hypoxia and L-glucose substitution (n = 6) by 671 +/- 14%. Comparison of hypoxia versus hypoxia and hypoglycemia conditions did not show them to be statistically different (P greater than 0.5). Lactate (10-1000 micrograms/ml) at a pH of 6.9 or 7.4 did not alter the action potential discharge frequency in corneal C fibers (n = 5, P greater than 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1998

Different neural mechanisms underlie dizocilpine maleate- and dopamine agonist-induced locomotor activity.

This study evaluated and compared the role of mesoaccumbens dopamine and the ventral pallidal region in the locomotor stimulatory action of the non-competitive N-methyl-D-aspartate antagonist dizocilpine maleate and dopamine agonists. Intra-accumbens injections of both amphetamine (1, 5 and 25 nmol) and dizocilpine maleate (1, 5, 25 and 50 nmol) induced a dose-dependent increase in locomotor activity. The N-methyl-D-aspartate antagonist was somewhat less effective than amphetamine. 6-Hydroxydopamine dopamine-depleting lesions of the nucleus accumbens completely blocked locomotor stimulation induced by focal administrations of amphetamine (5 nmol), but were ineffective in altering the actions of dizocilpine maleate (50 nmol). Ibotenic acid lesions of the ventral pallidal region and muscimol injections into this area also prevented the stimulatory effects of systemic amphetamine (1 mg/kg), while having no effect on the locomotor-activating actions of systemic dizocilpine maleate (0.3 mg/kg). Microdialysis studies revealed that systemically administered apomorphine (2 mg/kg) significantly decreased extracellular GABA in the pallidum, which was accompanied by substantial increases in locomotor output. Systemically administered dizocilpine maleate (0.3 mg/kg), on the other hand, also increased locomotor activity without having any effect on pallidal GABA. These data, taken together, indicate that while the locomotor effects of dopamine agonists are dependent upon intact mesoaccumbens dopamine and involve GABAergic efferents from the nucleus accumbens to the ventral pallidum, dizocilpine maleate's stimulatory actions are independent of such mechanisms.

Amphetamine↗
PubMed1992

Effects of a combination of acidosis, lactate, and lysophosphatidylcholine on action potentials and ionic currents in guinea pig ventricular myocytes.

The aim of this study was to determine the electrophysiological effects of a combination of factors that are of importance during myocardial ischaemia, i.e., acidosis, lactate, and lysophosphatidylcholine, in ventricular myocytes. Intracellular microelectrode techniques were used to record action potential and ionic currents in ventricular myocytes before, during, and after a 30 min exposure to a salt solution that was acidotic (pH 6.8), and contained lactate (10 mM) and lysophosphatidylcholine (5 microM). Single ventricular myocytes were dissociated enzymatically from guinea pig hearts, and perfused with either normal or modified physiological salt solution. Combined acidosis, lactate, and lysophosphatidylcholine resulted in a reduction in the resting membrane potential and maximum rate of depolarisation of phase 0, and flattening of the plateau but prolongation of the action potential duration at 90% repolarisation. Automatic activity was also induced in about one-third of the cells studied. Under voltage-clamp conditions, this combination of factors reduced the peak inward calcium current, on repolarisation after a depolarising step, reduced the steady-state outward current, and reduced the delayed rectifier current, measured as the tail current at the end of a depolarising clamp step. In some cells, a transient inward current was induced by the modified salt solution. It is concluded that the characteristic alterations in action potential characteristics induced by a combination of acidosis, lactate, and lysophosphatidylcholine are likely to result from reductions in the inward Ca current and the background and delayed rectifier K current.

Acidosis↗
PubMed2003

Pharmacology of valproate.

Valproate has been in clinical use for nearly 40 years for the treatment of a variety of neuropsychiatric illnesses, including bipolar disorder and epilepsy. Early reports linked its biochemical mechanism of action to alterations in gamma-aminobutyric acid (GABA)-ergic function. The definitive mechanism(s) mediating the clinical efficacy of this relatively simple molecule remain obscure. Although valproate does not directly interact with postsynaptic GABA receptors, it does increase regional neuronal concentrations of GABA by both inhibiting its metabolism and increasing its synthesis. The relevance of these effects to the clinical efficacy of valproate is unclear. Results of preclinical research, largely in rodents, have implicated ion channels, monoamines, corticotropin-releasing factor, and intracellular signaling proteins in the mechanism of action of valproate. This relative dearth of data in the area of valproate neuropharmacology is also evident when discussing the mechanism( s) of action of other mood stabilizers and anticonvulsants. Modern tools of basic and clinical neuroscience (eg, genomics, proteomics, functional brain imaging) will rapidly provide valuable insights into the precise mechanism(s) of action of valproate.

Animals↗
PubMed1996

Naloxone blockade of (-)pentazocine-induced changes in auditory function.

OBJECTIVE: In a previous report, we found that intravenous (i.v.) (-)pentazocine improved auditory sensitivity and significantly altered compound action potential (CAP) amplitudes. Its sigma (sigma)-receptor-selective optical isomer (+)pentazocine administered at the same dose was without effect, suggesting that the observed auditory neural effects might be mediated by an opioid receptor. To directly test this hypothesis, in the present investigation we attempted to antagonize the auditory neural effects of (-)pentazocine using the pure, nonspecific drug antagonist naloxone. DESIGN: In 25 normal-hearing, male, pigmented chinchillas, amplitude and latency changes in the click-evoked auditory nerve CAP (N1) and cochlear microphonic (CM) were tracked at six stimulus intensities during a baseline period and after the postbaseline administration of the opioid drug agonist (-)pentazocine (16 mg/kg; i.v.). In separate groups of chinchillas, (-)pentazocine was given alone or administered in combination with the standard opioid receptor antagonist naloxone administered at two doses. RESULTS: Robust changes in CAP amplitudes after (-)pentazocine occurred in the absence of measurable alterations in CAP response latencies, CM amplitudes, or blood chemistries and were significantly antagonized when naloxone (5 mg/kg) was added to the i.v. infusion. CONCLUSIONS: The observed blockade clearly indicates that the agonist effects of (-)pentazocine are opioid receptor-mediated and suggests a connection between opioid receptors and auditory neural function. Mechanisms of action and the connection between an opioid modulation of auditory function and stress, hyperacusis, and tinnitus are discussed.

Animals↗
PubMed1998

Effects of FK409, a nitric oxide donor, on renal responses to renal nerve stimulation in anesthetized dogs.

We examined the effects of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), a nitric oxide (NO) donor, on renal actions and norepinephrine overflow induced by renal nerve stimulation in anesthetized dogs, with or without N(G)-nitro-L-arginine (NOARG), a NO synthase inhibitor. Renal nerve stimulation at a low frequency (0.5-2.0 Hz) produced significant decreases in urine flow and urinary excretion of Na+ and increases in norepinephrine secretion rate. Renal nerve stimulation at a high frequency (2.5-5.0 Hz) which diminishes renal hemodynamics, elicited more marked decreases in urine formation and increases in norepinephrine secretion rate. Intrarenal arterial infusion of FK409 (0.25 microg/kg/min) failed to alter renal actions and increases in norepinephrine secretion rate in response to both low- and high frequency renal nerve stimulation. When NOARG (40 microg/kg/min) was administrated intrarenally, low-frequency renal nerve stimulation caused a potent antidiuresis and renal vasoconstriction. The renal nerve stimulation-induced increase in norepinephrine secretion rate was markedly enhanced by NOARG infusion. Simultaneous infusion of FK409 markedly attenuated the NOARG-induced enhancement of renal actions and increases in norepinephrine secretion rate, in response to low-frequency renal nerve stimulation. These results suggest that exogenous NO suppresses the renal nerve stimulation-induced norepinephrine overflow and renal actions in NO-depleted conditions. We also propose that endogenous NO functions tonically as an inhibitory modulator of renal noradrenergic neurotransmission.

Anesthesia↗
PubMed1988

Epileptiform discharges induced by altering extracellular potassium and calcium in the rat hippocampal slice.

During and after intense neuronal activity the concentration of extracellular potassium ([K+]o) increases while the concentration of calcium ([Ca2+]o) decreases. The present study examined the effect of increased [K+]o alone, and with a parallel decrease in [Ca2+]o, on overall excitability, long-term potentiation (LTP), and the appearance of epileptiform discharges. [K+]o and [Ca2+]o were varied over the range in which they fluctuate in vivo. Hippocampal slices were first equilibrated in a control artificial CSF containing 3.1 mM K+ and 1.5 mM Ca2+ and then reequilibrated in an identical solution except that the K+ was increased to 3.55, 4, 5, 6, or 8 mM with and without a decrease in Ca2+ to 1.0 mM. Raising [K+]o caused a leftward shift of input-output curves. Lowering [Ca2+]o to 1.0 mM had no effect on the ability of [K+]o to shift the input-output curve to the left. LTP was not changed by increasing [K+]o. Lowering [Ca2+]o to 1.0 mM blocked LTP and increasing the [K+]o did not overcome this blockade. When [K+]o alone was altered, the [K+]oS at which epileptiform bursts occurred 50% of the time were 5.6 and 7.6 mM for stimulus-locked and spontaneous bursting, respectively. The combination of decreased [Ca2+]o and increased [K+]o made slices considerably more prone to epileptiform activity. In 1.0 mM [Ca2+]o, the [K+]o at which 50% of the slices showed stimulus-locked bursting was decreased to 3.6 mM while that for spontaneous discharges was 5.4 mM. The sensitivity of hippocampal slices to [K+]o and [Ca2+]o, and the synergistic actions of alterations of these ions, indicates that even small changes in the aggregate extracellular ionic milieu may be important in epileptogenesis.

Animals↗
PubMed2002

Cellular action of thyroid hormone on the heart.

Changes in thyroid status markedly influence cardiac contractile and electrical activity. The predominant route by which triiodothyronine (T3) affects cardiac action is by exerting a direct effect in cardiac myocytes through binding to thyroid hormone nuclear receptor isoforms. In addition, T3 modifies cardiac action by alterations in the vascular system and decreases afterload of the left ventricle by subtle modification related to the sympathetic system. The importance of T3 nuclear receptor function has been further demonstrated by studies in null mutant mice in which thyroid hormone receptor-alpha (TRalpha) and thyroid hormone receptor-beta (TRbeta) or both are deleted. In mice with null mutations of the TRalpha, a markedly decreased heart rate and decreased contractile performance occurs in contrast to mice with deletion of TRbeta that have a normal heart rate and a normal contractile performance under baseline conditions. Thyroid hormone influences on heart rate are exerted by specific ion channel proteins in the sinus node of the left atrium. Some of these ion channels, such as the IF channel, the sodium/calcium exchanger protein, the L-type and T-type calcium channel, and the ryanodine channel are targets for thyroid hormone action. The increased contractile performance induced by T3 is largely mediated by increased expression of the calcium adenosine triphosphatase (ATPase) of the sarcoplasmic reticulum and decreased expression of phospholamban and T3 increases the phosphorylation status of phospholamban. The significant influence that is exerted by thyroid hormone signaling system related to contractile and electrical activity in the heart and the molecular basis for these alterations continues to be clarified.

Animals↗
PubMed2006

Guava extract (Psidium guajava) alters the labelling of blood constituents with technetium-99m.

Psidium guajava (guava) leaf is a phytotherapic used in folk medicine to treat gastrointestinal and respiratory disturbances and is used as anti-inflammatory medicine. In nuclear medicine, blood constituents (BC) are labelled with technetium-99m ((99m)Tc) and used to image procedures. However, data have demonstrated that synthetic or natural drugs could modify the labelling of BC with (99m)Tc. The aim of this work was to evaluate the effects of aqueous extract of guava leaves on the labelling of BC with (99m)Tc. Blood samples of Wistar rats were incubated with different concentrations of guava extract and labelled with (99m)Tc after the percentage of incorporated radioactivity (%ATI) in BC was determined. The results suggest that aqueous guava extract could present antioxidant action and/or alters the membrane structures involved in ion transport into cells, thus decreasing the radiolabelling of BC with (99m)Tc. The data showed significant (P<0.05) alteration of ATI in BC from blood incubated with guava extract.

Animals↗
PubMed2002

Emerging theories into the social determinants of health: implications for oral health promotion.

In recent years public health research has increasingly focused upon exploring the social determinants of health. This interest has partly arisen through an acknowledgement of the limitations of educational preventive approaches in improving population health and reducing health inequalities. Many health education interventions have been influenced by health behaviour research based upon psychological theories and models. These theories focus at an individual level and seek to explore cognitive and affective processes determining behaviour and lifestyle. Current psychological theories have only a limited value in the development of public health action on altering the underlying social determinants of health. New theoretical approaches have however, emerged which explore the relationship between the social environment and health. This paper aims to review and highlight the potential value to oral health promotion of three important public health theoretical approaches: life course analysis, salutogenic model and social capital. It is important that an informed debate takes place over the theoretical basis of oral health promotion. As the field of oral health promotion develops it is essential that it is guided by contemporary and appropriate theoretical frameworks to ensure that more effective action is implemented in the future.

Adaptation, Psychological↗
PubMed2001

The inhibitory action of quercetin on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells.

The effect of quercetin on lipopolysaccharide (LPS)-induced nitric oxide (NO) production was studied. Quercetin pretreatment significantly inhibited NO production in an LPS-stimulated RAW 264.7 murine macrophage cell line. Post-treatment with quercetin partially inhibited NO production. The inhibitory action of quercetin was due to neither the cytotoxic action nor altered LPS binding. The expression of inducible-type NO synthase (iNOS) was markedly down-regulated by quercetin. Quercetin suppressed the release of free nuclear factor (NF)-kappaB by preventing degradation of IkappaB-alpha and IkappaB-beta. Moreover, quercetin blocked the phosphorylation of extracellular signal regulated kinase 1/2 (Erk 1/2), p38, and c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) and, further, the activity of tyrosine kinases in LPS-stimulated RAW cells. Quercetin also inhibited interferon (IFN)-gamma-induced NO production. Taken together, these results indicate that the inhibitory action of quercetin on NO production in LPS- and/or IFN-gamma-stimulated macrophages might be due to abrogation of iNOS protein induction by impairment of a series of intracellular signal pathways.

Animals↗
PubMed2004

Anesthesia and sleep.

Although both general anesthesia and naturally occurring sleep depress consciousness, distinct physiological differences exist between the two states. Recent lines of evidence have suggested that sleep and anesthesia may be more similar than previously realized. Localization studies of brain nuclei involved in sleep have indicated that such nuclei are important in anesthetic action. Additional observations that regional brain activity during anesthesia resembles that in the sleeping brain have raised the possibility that anesthesia may exert its effects by activating neuronal networks normally involved in sleep. In animals, behavioral interactions between sleep and anesthesia appear to support these mechanistic similarities. Rat studies demonstrate that sleep debt accrued during prolonged wakefulness dissipate during anesthesia. Moreover, anesthetic potency is subject both to circadian effects and to the degree of prior sleep deprivation. Such interactions may partly explain anesthetic variability among patients. Finally, sleep and anesthesia interact physiologically. Endogenous neuromodulators known to regulate sleep also alter anesthetic action, and anesthetics cause sleep with direct administration into brain nuclei known to regulate sleep. Together, these observations provide new research directions for understanding sleep regulation and generation, and suggest the possibility of new clinical therapies both for patients with sleep disturbances and for sleep deprived patients receiving anesthesia.

Anesthesia, General↗