Comprehensive Assessment of the Time Course of Biomechanical, Electrophysiological and Neuro-Motor Effects after Botulinum Toxin Injections in Elbow Flexors of Chronic Stroke Survivors with Spastic Hemiplegia: A Cross Sectional Observation Study.

Botulinum neurotoxin (BoNT) is commonly used to manage focal spasticity in stroke survivors. This study aimed to a perform comprehensive assessment of the effects of BoNT injection. Twelve stroke subjects with spastic hemiplegia (age: 52.0 ± 10.1 year; 5 females) received 100 units of BoNT to the spastic biceps brachii muscles. Clinical, biomechanical, electrophysiological, and neuro-motor assessments were performed one week (wk) before (pre-injection), 3 weeks (wks) after, and 3 months (mons) after BoNT injection. BoNT injection significantly reduced spasticity, muscle strength, reflex torque, and compound muscle action potential (CMAP) amplitude of spastic elbow flexors (all p < 0.05) during the 3-wks visit, and these values return to the pre-injection level during the 3-mons visit. Furthermore, the degree of reflex torque change was negatively correlated to the amount of non-reflex component of elbow flexor resistance torque. However, voluntary force control and non-reflex resistance torque remained unchanged throughout. Our results revealed parallel changes in clinical, neurophysiological and biomechanical assessment after BoNT injection; BoNT injection would be more effective if hypertonia was mainly mediated by underlying neural mechanisms. BoNT did not affect voluntary force control of spastic muscles.

Cortical and spinal assessment - a comparative study using encephalography and the nociceptive withdrawal reflex.

BACKGROUND: Standardized objective methods to assess the analgesic effects of opioids, enable identification of underlying mechanisms of drug actions in the central nervous system. Opioids may exert their effect on both cortical and spinal levels. In this study actions of morphine at both levels were investigated, followed by analysis of a possible correlation between the cortical processing and spinal transmission. METHODS: The study was conducted after a double-blinded, two-way crossover design in thirty-nine healthy participants. Each participant received 30mg morphine or placebo as oral solution in randomized order. The electroencephalogram (EEG) was recorded during rest and during immersion of the hand into ice-water. Electrical stimulation of the sole of the foot was used to elicit the nociceptive withdrawal reflex and the reflex amplitude was recorded. RESULTS: Data from thirty subjects was included in the data analysis. There was no change in the activity in resting EEG (P>0.05) after morphine administration as compared to placebo. During cold pressor stimulation, morphine significantly lowered the relative activity in the delta (1-4Hz) band (P=0.03) and increased the activity in the alpha (8-12Hz) band (P=0.001) as compared to placebo. The reflex amplitudes significantly decreased after morphine administration (P=0.047) as compared to placebo. There was no correlation between individual EEG changes during cold pressor stimulation and the decrease in the reflex amplitude after morphine administration (P>0.05). CONCLUSIONS: Cold pressor EEG and the nociceptive reflex were more sensitive to morphine analgesia than resting EEG and can be used as standardized objective methods to assess opioid effects. However, no correlation between the analgesic effect of morphine on the spinal and cortical assessments could be demonstrated.

Short-term effects of a perinatal exposure to the HBCDD α-isomer in rats: Assessment of early motor and sensory development, spontaneous locomotor activity and anxiety in pups.

The present study investigated the developmental neurotoxicity of an early exposure to α-HBCDD through the ingestion of contaminated hen's egg in pregnant and lactating Wistar female rats. Hens were given α-HBCDD-contaminated feed (40 ng/g fresh matter) for 5 and 10 days, which produced eggs with HBCDD content of 33 and 102 ng/glipid weight, respectively. Female rats were administered daily p.o. with an appropriate volume of the whole egg from the day of fertilization (GD0) to the weaning day for pups (PND21). Fetuses and pups were thus exposed continuously to α-HBCDD via the dam over a whole 42-day period that included both gestation and lactation. The administered egg volume was calculated on the basis of daily egg consumption in humans (0.7 egg/person/day) and duration of gestation and lactation in both species, which led animals to be exposed to α-HBCDD at levels of 22 and 66 ng/kg/day, respectively. Neurobehavioral development of pups was investigated from PND3 to PND25 using various tasks including the righting reflex (PND4), the grasping reflex (PND5), the negative geotaxis (PND9), the forelimb grip strength test (PND10) and the locomotor coordination test (PND20). Pup ultrasonic vocalizations were also recorded daily from PND4 to PND14. After weaning, behaviors related to spontaneous locomotor activity and anxiety were examined in the open-field (PND25) and in an elevated-plus maze (PND26), respectively. The results showed a significant decrease in body weight of pups exposed to the lower HBCDD level from PND3 to PND28, whereas the weight of rat pups given 66 ng/kg/day of HBCDD was not different from controls. During the first 3 weeks of life, impairments in motor maturation of pups were observed in a dose-dependent manner depending on the test, whereas no significant differences were reported between male and female pups. At PND26, the anxiety level of female rats exposed to the lowest dose of HBCDD (22 ng/kg/day) was significantly reduced whereas it remained unchanged in males. No significant variations were measured in rats exposed to the higher level of HBCDD (66 ng/kg/day). These results suggest the potent developmental neurotoxicity of an early chronic exposure to the HBCDD α-isomer through the ingestion of hen's eggs contaminated with this pollutant and question the long-lasting consequences of this exposure on behavior abilities and brain functioning in adulthood.

Short-term effects of a perinatal exposure to a 16 polycyclic aromatic hydrocarbon mixture in rats: assessment of early motor and sensorial development and cerebral cytochrome oxidase activity in pups.

Humans are exposed to polycyclic aromatic hydrocarbons (PAHs), a family of ubiquitous neurotoxic pollutants, mainly through ingestion of contaminated food. Developing organisms can be exposed also to PAHs due to the ability of these compounds to pass through the placental barrier as well as through the breast milk. Previous animal studies have reported that the exposure of rats to a 16 PAH mixture at environmental doses strictly limited to gestation did not induce any long-lasting consequences, whereas gestational and lactational PAH exposure induced long-term behavioral and cerebral metabolic effects. In the present study, short-term effects of exposures to the same PAH mixture during gestation, or during gestation and lactation, were assessed by evaluating motor and sensory development of rat pups, and by measuring cerebral cytochrome oxidase activity (a marker of energetic metabolism) in different brain areas. Brain levels of PAHs and some monohydroxylated metabolites were also evaluated in pups at birth and at 21 days of postnatal life. No significant short-term modifications of behavioral development and of cerebral metabolism were observed following an early PAH exposure whatever the dose and the period of exposure. Surprisingly, the same brain levels of concentration of PAHs and metabolites were observed in control and exposed pups in both studies. These analytical results raise the difficulty in overcoming environmental contamination of control animals and the choice of such controls in experimental studies which focus on neurotoxicity of exposure to low levels of pollutants.

A re-assessment of treatment with a tyrosine kinase inhibitor (imatinib) on tissue sparing and functional recovery after spinal cord injury.

This study was undertaken as part of the NIH "Facilities of Research Excellence-Spinal Cord Injury" project to support independent replication of published studies. Here, we repeat key parts of a study reporting that rats treated with imatinib (Gleevec®, Novartis) after spinal cord contusion injury exhibited enhanced bladder function, greater recovery of motor function, and increased tissue sparing. Young adult female SCA Sprague-Dawley rats received moderate contusion injuries at T9-T10 using the MASCIS weight drop device. One group (n=16) received oral doses of imatinib 30min after injury and then daily doses for 5days. A control group (n=18) received vehicle. Motor function was assessed with the BBB locomotor rating scale and a contact plantar placement task. Bladder function was assessed by measuring the amount of urine retained in the bladder. Tissue preservation was assessed by immunostaining and stereological analysis. Rats that received imatinib had lower volumes of retained urine, suggesting improved bladder function, but there were no significant differences in motor function on any of the other tasks. Tissue preservation was assessed by immunostaining and stereological analysis. Quantitative analysis of spared tissue, cyst size, spared white matter, and inflammatory cell invasion revealed no significant differences between imatinib treated and control rats. Taken together our results confirm the findings that treatment with imatinib improves bladder function after SCI but fail to replicate findings of improved motor function, enhanced tissue sparing, and decreased inflammatory cell invasion.

Neurobehavioral assessment of mice following repeated postnatal exposure to chlorpyrifos-oxon.

Chlorpyrifos (CPF), one of the most widely-used organophosphorus (OP) insecticides in agriculture, is degraded in the field to its oxon form, chlorpyrifos-oxon (CPO), which can represent a significant contaminant in exposures to adults and children. CPO is also responsible for the acetylcholinesterase (AChE) inhibition associated with CPF exposures; CPF is converted by liver CYP450 enzymes to CPO, which binds to and inhibits AChE and other serine active-site esterases, lipases and proteases. Young children represent a particularly susceptible population for exposure to CPF and CPO, in part because levels of the plasma enzyme, paraoxonase (PON1), which hydrolyzes CPO, are very low during early development. While a number of studies have demonstrated developmental neurotoxicity associated with CPF exposure, including effects at or below the threshold levels for AChE inhibition, it is unclear whether these effects were due directly to CPF or to its active metabolite, CPO. PON1 knockout (PON1-/-) mice, which lack PON1, represent a highly sensitive mouse model for toxicity associated with exposure to CPF or CPO. To examine the neurobehavioral consequences of CPO exposure during postnatal development, PON1-/- mice were exposed daily from PND 4 to PND 21 to CPO at 0.15, 0.18, or 0.25 mg/kg/d. A neurobehavioral test battery did not reveal significant effects of CPO on early reflex development, motor coordination, pre-pulse inhibition of startle, startle amplitude, open field behavior, or learning and memory in the contextual fear conditioning, Morris water maze, or water radial-arm maze tests. However, body weight gain and startle latency were significantly affected by exposure to 0.25 mg/kg/d CPO. Additionally, from PNDs 15-20 the mice exposed repeatedly to CPO at all three doses exhibited a dose-related transient hyperkinesis in the 20-min period following CPO administration, suggesting possible effects on catecholaminergic neurotransmission. Our previous study demonstrated wide-ranging effects of neonatal CPO exposure on gene expression in the brain and on brain AChE inhibition, and modulation of both of these effects by the PON1(Q192R) polymorphism. The current study indicates that the neurobehavioral consequences of these effects are more elusive, and suggests that alternative neurobehavioral tests might be warranted, such as tests of social interactions, age-dependent effects on learning and memory, or tests designed specifically to assess dopaminergic or noradrenergic function.

Active emergence from propofol general anesthesia is induced by methylphenidate.

BACKGROUND: A recent study showed that methylphenidate induces emergence from isoflurane general anesthesia. Isoflurane and propofol are general anesthetics that may have distinct molecular mechanisms of action. The objective of this study was to test the hypothesis that methylphenidate actively induces emergence from propofol general anesthesia. METHODS: Using adult rats, the effect of methylphenidate on time to emergence after a single bolus of propofol was determined. The ability of methylphenidate to restore righting during a continuous target-controlled infusion (TCI) of propofol was also tested. In a separate group of rats, a TCI of propofol was established and spectral analysis was performed on electroencephalogram recordings taken before and after methylphenidate administration. RESULTS: Methylphenidate decreased median time to emergence after a single dose of propofol from 735 s (95% CI: 598-897 s, n = 6) to 448 s (95% CI: 371-495 s, n = 6). The difference was statistically significant (P = 0.0051). During continuous propofol anesthesia with a median final target plasma concentration of 4.0 µg/ml (95% CI: 3.2-4.6, n = 6), none of the rats exhibited purposeful movements after injection of normal saline. After methylphenidate, however, all six rats promptly exhibited arousal and had restoration of righting with a median time of 82 s (95% CI: 30-166 s). Spectral analysis of electroencephalogram data demonstrated a shift in peak power from δ (less than 4 Hz) to θ (4-8 Hz) and ß (12-30 Hz) after administration of methylphenidate, indicating arousal in 4/4 rats. CONCLUSIONS: Methylphenidate decreases time to emergence after a single dose of propofol, and induces emergence during continuous propofol anesthesia in rats. Further study is warranted to test the hypothesis that methylphenidate induces emergence from propofol general anesthesia in humans.

Assessment of luteolin (3',4',5,7-tetrahydroxyflavone) neuropharmacological activity.

Since the discovery that certain flavonoids (namely flavones) specifically recognise the central BDZ receptors, several efforts have been made to identify naturally occurring GABA(A) receptor benzodiazepine binding site ligands. Flavonoid derivatives with a flavone-like structure such as apigenin, chrysin and wogonin have been reported for their anxiolytic-like activity in different animal models of anxiety. Luteolin (3',4',5,7-tetrahydroxyflavone) is a widespread flavonoid aglycon that was reported as devoid of specific affinity for benzodiazepine receptor (BDZ-R) binding site, but its psychopharmacological activity is presently unknown. Considering (1) the close structural similarity with other active flavones, (2) the activity of some of its glycosilated derivatives and (3) the complexity of flavonoid effects in the central nervous system, luteolin was submitted to a battery of tests designed to evaluate its possible activity upon the CNS and its ability to interact with the BDZ-receptor binding sites was also analysed. Luteolin apparently has CNS activity with anxiolytic-like effects despite the low affinity for the BDZ-R shown in vitro. Our findings suggest a possible interaction with other neurotransmitter systems but we cannot rule out the possibility that luteolin's metabolites might show a higher affinity for the BDZ-R in vivo, thus eliciting the evident anxiolytic-like effects through a GABAergic mechanism.

Preclinical assessment of novel therapeutics on the cough reflex: cannabinoid agonists as potential antitussives.

Cough, a reflex defense mechanism, is a common symptom of many airway inflammatory diseases. At present there are no satisfactory treatments for cough that have an acceptable side effect profile. Recent data have described the inhibitory effect of selective cannabinoid CB(2) receptor agonists on sensory nerve activity in vitro and the cough reflex in a guinea pig model. CB(2) receptor expression is limited in the central nervous system (CNS) and hence the development of selective agonists may provide a new therapeutic strategy for treatment of cough devoid of the CNS-mediated side effects that are normally associated with nonselective cannabinoid agonists.

Assessment of the cough reflex after propofol anaesthesia for colonoscopy.

BACKGROUND: Dysfunction of the cough reflex as a result of the lingering effects of anaesthetics may lead to aspiration pneumonia or retained secretions after general anaesthesia. It is unknown whether low concentrations of propofol alter the cough reflex in the early period after anaesthesia. The objective of this study was to investigate the effect of low concentrations of propofol on the cough reflex sensitivity as assessed by the cough reflex threshold to an inhaled irritant. METHODS: Fifteen, ASA I-II, non-smoking patients undergoing elective colonoscopy were studied. Anaesthesia was induced and maintained with a blood target-controlled propofol infusion. Cough reflex threshold was measured with citric acid. Increasing concentrations of nebulized citric acid (2.5, 5, 10, 20, 40, 80, 160, 320, and 640 mg ml(-1)) were delivered during inspiration until a cough was evoked. The citric acid concentration eliciting one cough (C1) was defined as the cough reflex threshold. C1 was log transformed for statistical analysis (Log C1). Log C1 was measured before anaesthesia and during the recovery period with estimated decreasing propofol concentrations of 1.2, 0.9, 0.6, and 0.3 microg ml(-1). RESULTS: Log C1 (median; interquartile range) measured with propofol concentrations of 1.2, 0.9, 0.6, 0.3, and 0 microg ml(-1) were 1.9 (0.6), 1.9 (1.0), 1.9 (1.1), 1.9 (0.6), and 1.9 (0.7) mg ml(-1) (NS), respectively. However, light sedation was observed with propofol concentrations of 1.2 and 0.9 microg ml(-1). CONCLUSION: This study indicates that residual sedation after propofol anaesthesia for colonoscopy does not adversely affect the cough reflex.

Predictors of high ethanol consumption in RIIbeta knock-out mice: assessment of anxiety and ethanol-induced sedation.

BACKGROUND: Genetic and pharmacological evidence suggests that the cyclic adenosine monophosphate-dependent protein kinase A pathway modulates neurobiological responses to ethanol. Mutant mice lacking the RIIbeta subunit of protein kinase A (RIIbeta(-/-)) are resistant to ethanol-induced sedation and drink significantly more ethanol than littermate wild-type mice (RIIbeta(+/+)). We determined whether high ethanol intake by the RIIbeta(-/-) mice on alternate genetic backgrounds is reliably predicted by high basal levels of anxiety or resistance to the sedative effects of ethanol. METHODS: Two-bottle choice procedures and a battery of behavioral tests (elevated plus maze, open-field activity, and zero maze) were used to assess voluntary ethanol consumption and basal levels of anxiety in RIIbeta(-/-) and RIIbeta(+/+) mice on either a C57BL/6J or a 129/SvEv x C57BL/6J genetic background. Additionally, ethanol-induced sedation and blood ethanol levels were determined in RIIbeta(-/-) and RIIbeta(+/+) mice after intraperitoneal injection of ethanol (3.8 g/kg). RESULTS: RIIbeta(-/-) mice on both genetic backgrounds consumed more ethanol and had a greater preference for ethanol relative to RIIbeta(+/+) mice. However, RIIbeta(-/-) mice showed reduced basal levels of anxiety when maintained on the C57BL/6J background but showed increased anxiety when maintained on the 129/SvEv x C57BL/6J background. Consistent with prior research, RIIbeta(-/-) mice were resistant to the sedative effects of ethanol, regardless of the genetic background. Finally, RIIbeta(-/-) and RIIbeta(+/+) mice showed similar blood ethanol levels. CONCLUSIONS: These results indicate that high ethanol consumption is associated with resistance to the sedative effects of ethanol but that basal levels of anxiety, as well as ethanol metabolism, do not reliably predict high ethanol drinking by RIIbeta(-/-) mice.

Observer-rated ataxia: rating scales for assessment of genetic differences in ethanol-induced intoxication in mice.

Identification of genetic and physiological mechanisms underlying a drug's or mutation's effects on motor performance could be aided by the existence of a simple observation-based rating scale of ataxia for mice. Rating scales were developed to assess ataxia after ethanol (2.75, 3.0, and 3.25 g/kg) in nine inbred mouse strains. Each scale independently rates a single behavior. Raters, blinded to dose, scored four behaviors (splay of hind legs, wobbling, nose down, and belly drag) at each of four time points after injection. The severities of hind leg splaying and wobbling were quantifiable, whereas nose down and belly dragging were expressed in all-or-none fashion. Interrater reliabilities were substantial (0.75 0 at some time), but all doses were equally effective. Incidence of nose down and belly dragging behaviors increased strain dependently after ethanol, but strains did not differentially respond to dose. Ethanol-induced splaying was modestly, and negatively, genetically correlated with wobbling. Nose down and belly dragging tended to be associated with splaying and wobbling at later times. Four distinct ataxia-related behaviors were sensitive to ethanol. Strains differed in ethanol sensitivity for all measures. Modest strain mean correlations among behaviors indicate that these behaviors are probably under control of largely different genes and that ataxia rating scales should rate separate behaviors on discrete scales.

Quantitative assessment of directed hind limb scratching behavior as a rodent itch model.

Hind limb scratching is used increasingly as an itch model in rodents. Scratching is usually quantified as the number of scratching bouts over a 60 min period. Since the antipruritic effect of scratching should depend on the total time of skin contact, then the duration of scratching bouts and within-bout scratching frequency may also be important factors. Therefore, we measured these parameters during episodes of scratching directed toward the site (nape of neck) of intradermal injection of serotonin in Sprague-Dawley rats. Serotonin elicited significantly more scratching bouts than saline. There was a biphasic pattern of scratching over time, with peaks at 10-20 and 40-50 min. Although cumulative bout duration (2-min intervals) had a similar biphasic distribution, the mean individual bout duration (2.1 s) did not change significantly over time. Within-bout scratching frequency remained constant over time at 8 Hz. The number of scratching bouts was suppressed in a dose dependent manner by naltrexone (3 and 5 mg/kg), while the individual bout duration and the within-bout frequency were not significantly different compared with serotonin-evoked scratching without naltrexone. These results validate the total number of scratching bouts as an indicator of the magnitude of itch-related scratching.

Electromyographic assessment of blink and corneal reflexes during midazolam administration: useful methods for assessing depth of anesthesia?

BACKGROUND: There are at least three components of the anesthetic state: loss of consciousness, amnesia and obtundation of reflex responses to noxious stimuli. To investigate the third component, we used a standard electrical stimulus to evoke a blink reflex, which was electromyographically recorded. These data may give information on the anesthetic state. METHODS: The relation between the electrically evoked blink and corneal reflexes and the depth of sedation and anesthesia induced with intravenous midazolam was investigated. Ten patients received i.v. increments of midazolam (1 mg, 2 mg, 3 mg, 3 mg, 3 mg, etc., until a 21-mg total dose) to create a step-wise deepening of sedation and anesthesia. Depth of anesthesia was assessed by the Observer's Assessment of Alertness/Sedation (OAAS) scale, ranging from 5 ( = awake and alert) to 0 ( = no motor response to tetanic stimulation). RESULTS: Latency of the first (R1) and second (R2) blink components and the corneal (C) reflex component increased, whereas duration and area decreased with increasing depth of sedation and anesthesia. R1 was last seen at an OAAS score [mean (SD)] of 1.8 (0.8), R2 at a score of 3.1 (1.1), C at a score of 3.8 (0.8), and R3 at 4.8 (0.5). These end-points were all statistically different from each other, except R2 vs. C. CONCLUSIONS: Our results suggest that the differential sensitivity of the components of the blink reflex could be useful to monitor depth of sedation and light levels of anesthesia during the administration of midazolam.

Conditions for insertion of the laryngeal mask airway: comparisons between sevoflurane and propofol using fentanyl as a co-induction agent. A pilot study.

BACKGROUND AND OBJECTIVE: To compare the conditions for insertion of the laryngeal mask airway using sevoflurane or propofol plus fentanyl. We evaluated the haemodynamic changes and cost of induction of anaesthesia in both groups. METHODS: Sixty patients were equally and randomly divided into two groups. Both groups received fentanyl 1 microg kg(-1). Patients in the sevoflurane group were induced with 8% sevoflurane and those in the propofol group with propofol 2.5 mg kg(-1). Conditions for insertion were graded on a three-point scale using six variables. Overall, conditions were assessed as excellent, satisfactory or poor based on the total score in each group. Systolic and diastolic arterial pressure and heart rate were recorded for 6 min after mask insertion. The financial cost of induction in both groups was calculated. RESULTS: The mean (+/- SD) time taken from induction to successful laryngeal mask insertion was significantly shorter with propofol (68.70 +/- 22.60 s) compared with sevoflurane (149.83 +/- 55.25 s). Excellent or satisfactory conditions were observed in 30 (100%) patients in the propofol group and in 29 (96.66%) in the sevoflurane group. Systolic and diastolic arterial pressures were significantly lower in the propofol group. The cost of sevoflurane used was 3.95 euros +/- 1.48 (Rs 216.23 +/- 64.66) (P < 0.05) compared with that of propofol, which was 3.23 euros +/- 0.65 (Rs 141.00 +/- 28.20). CONCLUSIONS: Although there was a faster induction with propofol-fentanyl, conditions for insertion of the laryngeal mask airway were similar in both groups. Haemodynamic stability was better with sevoflurane-fentanyl. The propofol-fentanyl combination was more cost-effective.

Electrophysiological assessment of the effect of intrathecal baclofen in spastic children.

OBJECTIVES: To evaluate the effect of intrathecal baclofen in a group of spastic children using electrophysiological procedures described in adults. METHODS: Six children (aged 1-14 years) with severe spasticity of various aetiologies underwent transcranial magnetic stimulation, H reflex and flexor reflex studies before and after intrathecal injection of baclofen. Ashworth scale was used for clinical evaluation of spasticity. RESULTS: Motor evoked potentials, present in two patients before baclofen, were preserved after injection. Before baclofen, H reflex was present in 5 patients (H(max)/M(max) from 0.23 to 0.84) and absent in one who had infantile neuroaxonal dystrophy. After baclofen, it was absent in 4 patients and markedly reduced in one. Surface of flexor reflex significantly decreased after baclofen (P=0.01), while threshold significantly increased (P=0.003). CONCLUSIONS: In spastic children, the action of baclofen on spinal pathways may be quantified by the same electrophysiological procedures as in adults. This approach may contribute to select optimal dosage.

EEG evaluation of reflex testing as assessment of depth of pentobarbital anaesthesia in the rat.

Electroencephalography (EEG) was applied to evaluate the validity of the paw pinch reflex as an indicator of anaesthetic depth in rats which are anaesthetized with a single intraperitoneal dose of pentobarbital. After induction of the anaesthesia, characterized by the rapid loss of the animals' ability to maintain upright posture, the EEG of 10 out of 11 rats was dominated by paroxysmal (burst suppression) activity, associated with unconsciousness. In seven out of 11 rats, the paw pinch reflex was lost after onset of paroxysmal electroencephalographic activity. However, the paw pinch reflex remained present in four out of 11 animals, demonstrating that the response is independent of cortical activity. In five out of seven rats, the EEG still showed paroxysmal activity when the paw pinch reflex was regained. However, in two other rats the EEG returned to a pattern similar to that shown by awake animals, 4 and 21 min respectively, before the reflex was regained. These data indicate that in the pentobarbital-anaesthetized rat, presence of the paw pinch reflex is not related to the level of depression of electrical activity in the cerebral cortex, and consequently is probably not related to the level of consciousness. Based upon these findings it is concluded that the paw pinch reflex is unreliable as a sole indicator of anaesthetic depth.

Continuous total intravenous anesthesia, using propofol and fentanyl in an open-thorax rabbit model: evaluation of cardiac contractile function and biochemical assessment.

Effects are reported of an anesthetic protocol involving use of predetermined intravenous (i.v.)-administered drug doses during acute experimental procedures in vagotomized, New Zealand White rabbits with open thorax (n = 20) in a nonsurvival study. After induction of anesthesia by intramuscular (i.m.) administration of ketamine hydrochloride (25 mg/kg of body weight) and xylazine hydrochloride (15 mg/kg), continuous total intravenous anesthesia (TIVA) with propofol (0.6 mg.kg-1.min-1), fentanyl (0.48 micrograms.kg-1.min-1) and the neuromuscular agent vecuronium bromide (0.003 mg.kg-1.min-1) was maintained. Oxygenation conditions, acid-base balance, biochemical and hemodynamic variables, and cardiac contractile function were assessed. Measurements were made and blood analysis was done at the moment of ear vein catheterization (P1); before (P2) and after (P3) sternotomy; after complete instrumentation (P4); and at the beginning (T1), in the middle (T2), and at the end (T3) of the experimental protocol. From T1 to T3, heart rate was kept constant by use of atrial pacing at a rate of 235 +/- 15 beats/min. During surgical preparation and instrumentation, hemoglobin (Hb) concentration decreased from 12.5 +/- 0.9 g/dl (mean +/- SEM) to 7.7 +/- 0.7 g/dl and remained stable thereafter. Blood gas analysis (PO2, PCO2, pH, HCO3-, base excess, measured SaO2) and measurement of plasma lactate concentration revealed constant, adequate oxygenation. Plasma electrolyte values (Na+, Cl-, K+, Ca2+) remained within physiologic ranges throughout. Blood glucose concentration increased from 229 +/- 30 mg/dl at P1 to 382 +/- 34 mg/dl at P3. At T1, glycemia had returned to normal values and remained stable. Heart rate, blood pressure, ventricular elastance (Ees), and diastolic stiffness constant (Kc) remained stable throughout. Other indices of ventricular function (dP/dtmax, thickening, ejection duration, and maximal left ventricular pressure) remained unaltered as well. Left ventricular relaxation (dP/dtmin, tau) did not change. After anesthesia induction by i.m. administration of ketamine and xylazine, TIVA with predetermined drug dosages of propofol and fentanyl provided stable cardiovascular function for open-thorax long-term experimental observations in a nonsurvival setting.

The effects of incentive on antisaccades: is a dopaminergic mechanism involved?

The effect of incentive was investigated upon performance in the antisaccade (AS), memory saccade (MS) and reflexive saccade (RS) task, alone and following performance in tasks of a psychometric battery. Accuracy performance (correct saccades) in the AS and MS task is dependent on two prefrontal functions, the preservation of transient information across short time intervals and the inhibition of prepotent but inappropriate responses, and is impaired in patient populations with known prefrontal dysfunction. It was predicted that, in normal humans, incentive will improve accuracy performance in the AS and MS task, leaving performance in the RS task unaffected (study 1). Saccades were recorded in 24 healthy young male volunteers. Measurements of saccades were performed (in the presence and absence of monetary incentive) alone or following performance on a psychometric test battery that included tasks of working memory, vigilance, attention and psychomotor activity. Incentive increased the number of correct saccades in the AS task and the performance index in the working memory task. No other direct changes were seen in the presence of incentive. The role of dopamine in performance in the AS compared to the RS task was investigated subsequently in study 2. Twenty healthy young male volunteers received levodopa and benserazide (100 and 25 mg, respectively) orally, and 1 and 5 h later measurements of AS and RS were performed. Levodopa significantly decreased the number of correct saccades in the AS task. No other effects were seen. These data, taken together, suggest, first, that the accuracy performance in the AS task is more sensitive than in the MS or RS task, to positive incentive due to monetary reward; and second, that the dopaminergic system may mediate such an effect, because levodopa, a dopaminergic drug, influenced the same performance measurement. The relationship, however, between these two manipulations (incentive and administration of dopaminergic drugs) is not clear, because incentive improved and levodopa impaired performance.