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Biomedical subjects

G A Lucas

Publications and source records attributed to G A Lucas.

At least 19 recordsLinked to original sources

Generation and phenotypic characterization of a galanin overexpressing mouse.

In most parts of the peripheral nervous system galanin is expressed at very low levels. To further understand the functional role of galanin, a mouse overexpressing galanin under the platelet-derived growth factor-B was generated, and high levels of galanin expression were observed in several peripheral tissues and spinal cord. Thus, a large proportion of neurons in autonomic and sensory ganglia were galanin-positive, as were most spinal motor neurons. Strong galanin-like immunoreactivity was also seen in nerve terminals in the corresponding target tissues, including skin, blood vessels, sweat and salivary glands, motor end-plates and the gray matter of the spinal cord. In transgenic superior cervical ganglia around half of all neuron profiles expressed galanin mRNA but axotomy did not cause a further increase, even if mRNA levels were increased in individual neurons. In transgenic dorsal root ganglia galanin mRNA was detected in around two thirds of all neuron profiles, including large ones, and after axotomy the percentage of galanin neuron profiles was similar in overexpressing and wild type mice. Axotomy reduced the total number of DRG neurons less in overexpressing than in wild type mice, indicating a modest rescue effect. Aging by itself increased galanin expression in the superior cervical ganglion in wild type and transgenic mice, and in the latter also in preganglionic cholinergic neurons projecting to the superior cervical ganglion. Galanin overexpressing mice showed an attenuated plasma extravasation, an increased pain response in the formalin test, and changes in muscle physiology, but did not differ from wild type mice in sudomotor function. These findings suggest that overexpressed galanin in some tissues of these mice can be released and via a receptor-mediated action influence pathophysiological processes.

Adrenal Glands↗

Extracellular cholecystokinin levels in the rat spinal cord following chronic morphine exposure: an in vivo microdialysis study.

Conflicting results concerning the issue of whether or not chronic morphine exposure induces an increase in CCK biosynthesis have been found in many CNS sites, including the spinal cord, where CCK activity may contribute to the facilitation of the development of opiate tolerance. The present study was undertaken in order to monitor the extracellular level of CCK under spontaneous and stimulus-evoked release in the spinal cord dorsal horn of drug naive and morphine tolerant rats. Tolerance was induced by implantation of two morphine pellets (2x75 mg) which induced a stable morphine plasma concentration after 48 h post-implantation. The tail-flick test and naloxone precipitated withdrawal were used as indexes of tolerance and dependence to morphine. The effect of morphine-pellet implantation on basal and K+-induced release of CCK-like immunoreactivity (CCK-LI) in the rat dorsal horn were monitored with in vivo microdialysis 96 h after implantation of morphine or placebo pellets, when rats showed tolerance and dependence. Basal CCK levels were below the detection limit of the assay (0.6 pM) in both tolerant and normal animals. K+ (100 mM) in the perfusion medium induced a more than 3-fold increase of the extracellular level of CCK-LI in control animals, and a more than 4-fold increase on CCK-LI in morphine-pellet implanted animals. However, this difference was not significant. In addition, naloxone (2 mg/kg; i.v.), did not induce any change in the extracellular level of CCK in either group. The present study suggests that the modulatory interaction between CCK and opioids in the development of tolerance in the spinal cord may occur without necessarily increasing the extracellular level of CCK. Another possible explanation of the finding is that the microdialysis technique is not sensitive enough to detect differences in unstimulated CCK levels in normal and tolerant animals.

Analgesics, Opioid↗

On the role of cholecystokinin in the mediation of spinal reflex excitability in intact and axotomized rats.

The effects of intrathecal (i.t.) administration of cholecystokinin (CCK) on the hindlimb flexor withdrawal reflex were compared in decerebrate, spinalized, unanaesthetized rats with intact sciatic nerves or 14-26 days after unilateral transection of the sciatic nerve. The effect of CI-988, a CCK-B receptor antagonist, on the facilitation of the flexor reflex induced by conditioning stimulation (CS) of C-afferents was also examined. Intrathecal CCK induced facilitation of the flexor reflex over the dose range of 10 ng-1 micrograms in rats with intact and sectioned sciatic nerves. However, the facilitation induced by CCK in axotomized rats was significantly reduced compared with nerve intact animals. CI-988 did not block the facilitation of the flexor reflex induced by the CS and the increases in reflex magnitude during the CS train (wind-up) in rats with intact and sectioned sciatic nerves. The present results indicate that the excitatory effect of CCK on the spinal cord is reduced after axotomy, suggesting that nerve section may induce transsynaptic changes in the spinal cord leading to hyposensitivity to CCK. Furthermore, it is suggested that CCK may not play a significant role in the phenomenon of wind-up and central sensitization after repetitive C-fiber input under normal conditions or after axotomy, when expression of CCK and CCK-B receptors are increased in sensory neurons.

Animals↗

Pressure algometry in healthy subjects: inter-examiner variability.

The purpose of this study was to estimate inter-examiner reliability of head and neck algometry. Pain perception thresholds were assessed with a mechanical pressure algometer in 21 healthy individuals. Thresholds were assessed at 13 symmetrical points on each side of the head and neck, at the deltoid muscle and at the median finger. The pressure range of the instrument proved insufficient to study the pain perception threshold on the finger, however. Two different examiners carried out one or two examinations in each subject during one day. The sequence of investigations was varied randomly. The inter-examiner reliability was found to be good, with a mean intra-class correlation coefficient (ICC) of 0.75. Intra-examiner reproducibility was excellent (mean ICC = 0.84). The mean inter-examiner coefficient of variation was 18.7%, while the mean coefficient of repeatability (CR) was 1.60 kg/cm2. In comparison, the mean intra-examiner coefficient of variation was 15% while the mean CR was 1.29 kg/cm2. Statistically significant differences between examiners were found for the frontal point (p < 0.01), while a trend towards lower thresholds in one of the two observers was seen in 10 of the 13 non-significant points. Inter-examiner reliability of side differences was excellent, with CR = 1.23 kg/cm2. In conclusion, manual algometry with a rather inexpensive mechanical device has a good to excellent inter-rater reliability. When studying patients, however, the possible bias introduced by different examiners should be taken into account, both regarding study design and data analysis.

Adult↗

Relaxation of human temporal artery by endothelin ETB receptors.

Endothelin receptors have been characterized in human temporal artery by molecular biological methods and in vitro pharmacology. Reverse transcriptase-polymerase chain reaction was used to detect mRNA encoding ETA and ETB receptors in normal and endothelium-denuded arteries. Vasomotor response experiments with a specific ETA antagonist (FR 139317) suggested the presence of ETA subtypes. Marked ETB-mediated relaxation was obtained with ET-3 when ETA activity was blocked in precontracted arteries. Relaxation was significantly reduced by bosentan, indomethacin, and a nitric oxide synthase inhibitor. It may be speculated that the relaxant activity is mediated through ETB1 receptors.

Azepines↗

[Micro-mesoscopic study of the lateral wall of the human cavernous sinus].

The authors studied the structures of human cavernous sinus in its interior as well as on the lateral wall, utilizing thick, frontal, sequential sections. They show the significance of this wall, frequently used as surgical accessway to diseases encountered within this venous structure of the dura-mater.

Abducens Nerve↗

Negative anticipatory contrast and preference conditioning: flavor cues support preference conditioning, and environmental cues support contrast.

In 2 experiments, access to a 0.15% saccharin solution was followed on alternating days by access to a 32% sucrose solution and the same saccharin solution. In Experiment 1, rats increased both intake of and preference for a flavored saccharin solution that predicted sucrose, but neither effect was found using a predictive odor cue alone. Experiment 2 replicated the predictive flavor results but showed suppression of saccharin intake when environmental cues predicted sucrose. When both flavor and environment predicted sucrose, saccharin intake did not change, but preference for the predictive flavor increased. Discriminative taste cues appear to facilitate the development of preference conditioning, but environmental cues favor negative anticipatory contrast effects. Also, preference conditioning and contrast may develop concurrently and compete for expression.

Animals↗

Morphology, distribution and types of valves in the adult male's testicular veins.

Morphologically, the pampiniform plexuses investigated had, in their majority, no vascular spiraling on the left side, the same occurring on the right side; however, as for the total number of valves, except for those of the pampiniform plexuses, the left side was found contain a greater number of valves. As regards valve types, there is a predominance of double semilunar one on both sides rather than single semilunar valves.

Adult↗

[Micro-mesoscopic study of fibro-muscular structures of the venous nephro-adrenal transition in humans].

The purpose of this work has been to study the disposition of the fiber and muscular tissues of the wall of the supra-renal left vein, and of its transition to the renal vein. We analysed the disposition of the bundles of muscular, collagenic, elastic and myoelastic fibers, and how they integrate from a morpho-functional point of view. In a general way, we evidence the presence of strong longitudinal musculature in the venous wall, and condensations of the collagenic tissue at the level of the ostium of the mouth which constitutes real pillars of sustain of the bundles of the muscular fibers. In relation to the venous transition we concluded that, the morpho-functional architecture of the region, do not suggest the existence of a morphological sphincter but, in fact of the physiological sphincter.

Adolescent↗

[A micromesoscopic study of human arachnoid granulations].

The functional anatomy of the arachnoid granulations of the upper sagittal sinus was studied by means of micromesoscopic techniques in order to contribute to elucidating aspects of drainage pathways of the cerebrospinal fluid through their fibrous components. The arrangement of fibrous elements was analysed at the base of the peduncle, peduncle, middle and apex of granulation. The analysis of serial sections shows collagen bundles at the base of the peduncle with a predominantly circular morphology, longitudinally directed towards the peduncle's longest axis. These bundles arise in the middle of the granulation, them branch off towards its apex and periphery. The elastic bundles present an arrangement similar to that described for collagen bundles, delimiting with such bundles intercommunication channels from the base of the peduncle up to the apex of the granulation. Bundles of reticular fibers arranged in between the collagen meshes were found at the base of the peduncle. The fibrous capsule of granulation is composed of collagen bundles and a small number of elastic fibers.

Adult↗

Anticipation of future food: suppression and facilitation of saccharin intake depending on the delay and type of future food.

A series of studies examined the (Sprague-Dawley) rat's tendency to suppress intake of .15% saccharin when it was followed by a second food after 4-, 16-, or 32-min delays. The second foods examined were 32% sucrose, 64% sucrose, lab chow, a Nutrasweet solution, skim milk, and chocolate milk. Saccharin intake was influenced by both the delay and the specific food available. Subsequent analysis showed that saccharin intake before the 4-min delay was an inverse function of the caloric value of the second food. However, saccharin intake before the 16-min delay was better predicted as an inverse function of the hedonic value of the second food. The results suggest that the caloric and hedonic values of a food may influence food selection across different time courses, and that the effective time horizon for the sequential comparison of foods depends on the specific foods that are compared.

Animals↗

Learning and meal-associated drinking: meal-related deficits produce adjustments in postprandial drinking.

Two experiments examined the effect of meal-related water deficits on the distribution of meal-associated drinking. In the first procedure free-feeding rats received 10-, 20-, or 30-min delays between the end of a meal and the subsequent availability of postprandial water. Each delay condition remained in effect for 10 consecutive days. The primary effect of the delay was to postpone the intake of postprandial drinking. None of the delay conditions produced an increase in preprandial drinking. However, when the rats were returned to baseline following the delay conditions a pronounced rebound effect was obtained in the proportion of postprandial drinking. The second experiment followed the same general procedure except that 5-min access to water was always presented after each meal and before the postprandial water restrictions. Under this procedure the rats increased their water intake during the 5-min period when the postprandial restrictions were imposed. These findings show that meal-related water deficits can affect the timing and proportion of postprandial drinking, but provide no evidence that meal-related deficits increase preprandial drinking. The results suggest that the anticipation of meal-related water deficits may play a role in shaping the rat's postprandial drinking pattern.

Animals↗

Anticipatory drinking in rats: compensatory adjustments in the local rate of intake.

The current experiment examined whether dehydrated rats could learn to anticipate disruption of access to water. Previous research showed that rats running in a wheel in order to drink compensated for local disruptions on intake by increasing their rate of intake after, but not prior to the initial disruption. The present experiment exposed rats to either a fixed-ratio (FR) schedule that required rats to run in order to drink or a matched, fixed-time (FT) schedule that allowed the animals intermittent access to water without running. Access to water was disrupted by restricting the quantity of water available per drink bout. Rats increased their local rate of water intake prior to the disruption under the FT schedule but not under the FR schedule. The results suggest that rats can learn to increase their local rate of intake in anticipation of local restrictions on water under response-independent (FT) schedules. It was hypothesized that these anticipatory increases in the local rate of intake resulted from a priming effect due to the motivating effects of stimuli associated with water and/or frustration resulting from attempts to drink prior to water availability.

Animals↗

Interpellet delay and meal patterns in the rat.

Rats typically eat in short discrete meal periods separated by long intermeal intervals. The present study measured meal patterns and total intake of food and water when the rate of access to food pellets within the meal was reduced by delaying the time between pellet deliveries. In contrast to studies that reduce the caloric density of food, simple interpellet delay produced a marked reduction in meal size at the shorter (32 sec or less) interpellet delays. However, longer delays (up to 128 sec) produced no further change in average meal size. The results suggest that meal size is determined (1) by a positive feedback component with a relatively short decay time probably based on gustatory stimulation from feeding, and (2) by a negative feedback component capable of integrating total intake across delays of up to 1 hour. Increasing the delay between pellets appeared to interfere with the positive feedback component, but not with the negative feedback component.

Animals↗

Time horizons in rats: the effect of operant control of access to future food.

The primary goal of this experiment was to determine whether the addition of an operant requirement for access to a less costly (continuous reinforcement) patch of future food increased the time horizon over which that future patch decreased intake in a currently available depleting (progressive-ratio) patch. Three groups of 4 rats were tested. Each member of the earned-time group was required to cumulate a fixed-time outside the progressive-ratio patch to obtain access to food in the less costly patch; the fixed-time requirement ranged from 2 to 64 min. Rats in the matched-time group received response-independent access to less costly food at the average delay shown by the earned-time group. Rats in the matched-time no-food group were removed from the chamber at the same average delay without receiving access to less costly food. Two of the earned-time rats showed an increased time horizon relative to that shown by the matched-time rats (approaching 40 min for 1 rat). The other 2 earned-time rats markedly increased instrumental responding but showed suppression of intake only when food was less than 20 min away. The matched-time group showed less suppression of intake over a similar range of delay intervals. Surprisingly, the matched-time no-food animals also showed suppression of intake concentrated at the end of the session, possibly reflecting the receipt of their entire daily ration 30 min after the session. The potential importance of time horizons to the foraging process is clear, but experimenters are still working out paradigms for investigation of these horizons.

Animals↗

Time horizons in rats foraging for food in temporally separated patches.

An important tenet of optimal foraging theory is that foragers compare prey densities in alternative patches to determine an optimal distribution of foraging behavior over time. A critical question is over what time period (time horizon) this integration of information and behavior occurs. Recent research has indicated that rats do not compare food density in a depleting patch with that in a rich patch delayed by an hour or more (Timberlake, 1984). In the present research we attempted to specify over what time period a future rich patch would affect current foraging. The effect of future food was measured by early entry into the rich patch (anticipation) and by a decrease in food obtained in the depleting patch (suppression). The rats showed anticipation of a rich patch up to an hour distant, but suppressed current feeding only if the rich patch was 16 min distant or less. The suppression effect appeared mediated by competition for expression between anticipatory entries into the rich patch and continued foraging in the depleting patch. These results suggest that optimal foraging is based on a variety of specific mechanisms rather than a general optimizing algorithm with a single time horizon.

Animals↗

System-specific differences in behavior regulation: overrunning and underdrinking in molar nondepriving schedules.

In two experiments we tested the molar regulation prediction that animals adjust schedule performance to reduce deviations from baseline response totals. Both experiments constrained the baseline drink-burst length under molar nondepriving schedules but allowed rats to continue running without drinking. In Experiment 1, rats were required to run in order to drink. In Experiment 2, water was delivered independently of running by fixed-time (FT) schedules. Under the run-to-drink contingency, rats exceeded their baseline amounts of running (overrunning) but failed to maintain their baseline water intake (underdrinking). The total amount of running that did not lead to drinking approximated baseline running. Under the FT schedules, rats again underdrank, but total running approximated baseline. These results do not support previous studies that have shown molar equilibrium effects under nondepriving reciprocal schedules. We conclude that (a) contingent running may not substitute for independent running; (b) intermittent access to water reduces the total instigation for drinking; (c) molar regulation differs under reciprocal and nonreciprocal schedules; and (d) more dynamic, system-specific regulatory models need to be developed.

Animals↗

Schedule constraint on the average drink burst and the regulation of wheel running and drinking in rats.

Two experiments compared predictions of a molar-pattern model and a general molar behavior regulation model by requiring rats to wheel run for access to water. In both experiments schedule parameters constrained the baseline average burst length of drinking without constraining total drinking. Five levels of schedule constraint were imposed on time spent per drinking burst (Experiment 1) or the number of drinks per burst (Experiment 2). The results of both experiments supported the general molar behavior regulation view but not the molar-pattern model by showing no increase in total wheel running and no decrease in total drinking under schedule constraint. However, both experiments also showed local effects of drink burst constraint, including a direct relation between the degree of constraint and the local rate of drinking, and an approximation of the temporal distribution of baseline drinking under all degrees of schedule constraint. Most local changes support the view that rats defend the baseline temporal distribution of responding under schedule constraint, though some changes appear related to disruption of local response pattern characteristics.

Animals↗