Licking during forced spout alternation in rats: resetting the pacemaker or disconnecting the motor output?

Summary Rats trained to alternate between two adjacent drinking spouts (each spout is retracted after a single lick and presented again after the animal has licked at the other spout) emit 2.5 licks instead of the optimum 1 lick per spout presentation. The question whether the pacemaker of licking is reset or continues to run during transition between spouts was addressed in three experiments performed in 10 highly overtrained rats. Videorecording analysis of oro-facial activities showed that the rat's mouth was firmly closed during the 500 ms transition between spouts. EEG was recorded from the region of hypoglossal nucleus with implanted bipolar electrodes during continued licking at one spout and during spout alternation. Averaging (n = 256, 1024 ms) centered around the onset of the first lick at the newly contacted spout showed 2–3 lick related potentials in the post-transitional interval whereas only one such wave occasionally appeared at the end of the pre-transition period. Computer plotted distributions of post-transition licks (timed with respect to the last pre-transition lick) were examined while the horizontal or vertical distance between spouts was increased. Growing spout separation changed the height but not the timing of the modes of the post-transition lick distribution. This phase-locked synchronization of pre- and post-transition licks indicates that the central timing network of the lick generator is not reset but continues to run during transition between spouts and that the cessation of tongue movements is due to inhibition of the intracycle pattern generator and motor output. It is concluded that more sensitive recording techniques are required to detect the activity of the central timing network in absence of overt licking.     

Measurement of licking response execution in the rat

Two procedures for analysis of the licking response execution in rats are described. In both procedures, the pressure of the animal's tongue upon the water spout was transmitted on a pressure transducer and voltage analog of the licking response was analyzed. With the first arrangement, a signal averager was used and the licking response emission could be described in terms of time integral of force. In the second arrangement, an on-line computer was used and parameters of response duration, peak force, and interlick interval were added. Use of these measures in investigation of problems related to initiation, execution, and regulation of the licking response is discussed.     

Representation of the body in the lateral striatum of the freely moving rat: single neurons related to licking

This study examined the relationship of single-neuron activity (n = 739), recorded from the lateral striatum of freely moving rats, to oral movements involved in licking single drops of liquid. Certain neurons (n = 74) fired specifically in relation to licking. Their firing rates increased during licking, but remained near zero in the absence of licking, throughout a full sensorimotor examination of the remainder of the orofacial area and all other body parts. Another category of neurons (n = 17) fired during licking but also fired in the absence of licking, during one or more other orofacial sensorimotor function(s). Lick-related neurons were located in the lateral striatum, throughout the entire anterior-posterior range studied (from +1.5 to -1.5 mm anterior-posterior, A-P, bregma = 0). Summed over the full A–P range, they were located significantly ventral to representations of the trunk and limbs. These findings extend the characterization of the somatotopic organization exhibited by lateral striatal neurons in the rat, to include representation of oral functions, consistent with converging evidence regarding the functional organization of the striatum.     

Effects of subdiaphragmatic vagotomy on schedule induced drinking and schedule dependent lever pressing

Fourteen male albino rats reduced in body weight were exposed to a daily 1 hr FI-1 min schedule of food reinforcement. When schedule induced licking and drinking and schedule dependent lever pressing stabilized, seven animals were subjected to bilateral subdiaphragmatic vagus nerve transections and the other seven animals were subjected to sham operations. Changes in licking, drinking, and lever pressing were assessed when animals were reduced to 80% of their initial body weight by partial food deprivation and when body weights recovered after the animals were returned to conditions of ad lib feeding. Results indicate that vagotomy produces a significant decrease in schedule induced licking and drinking when animals are at reduced body weight. When vagotomized rats are allowed to recover body weight due to ad lib feeding, lever presses decrease but licking and drinking are not further reduced. The sham operation had no appreciable effects at reduced body weight. When allowed to recover body weight sham animals exhibited significant decreases in licking, drinking, and lever pressing. In addition, the rate of body weight gain and home cage food and water consumption and water consumed in response to hypertonic saline injections were reduced in vagotomized animals when allowed to feed ad lib. Results are discussed in terms of vagal afferent activity from the viscera to the lateral hypothalamus associated with food deprivation and body weight reduction and the maintenance of adjunctive behavior.     

Microstructural Analysis of the Ingestive Behavior of the Rat Ingesting Polycose

A microstructural analysis of the ingestive behavior of rats ingesting seven concentrations of Polycose, was undertaken in an attempt to understand how this complex mix of mono-, di-, and polysaccharides controls their ingestive behavior. In every respect, the pattern of results resembled those obtained using mono- and disaccharides. Over a concentration range of 0.6% to 40%, the volume ingested was a nonmonotonic function of concentration, the duration of the meal was a linear decreasing function of concentration, the initial rate and the rate of decline of the rate of licking were increasing linear functions of the log of the concentration, cluster size was a linear increasing function of log concentration, and the proportion of short intercluster intervals increased linearly with the log of the concentration. These results support the view that the control that Polycose exerts on the ingestive behavior of the rat is very similar to that exerted by mono- and disaccharides.     

A simple method of monitoring licking responses that is compatible with electrophysiological recording

A simple technique is described for the monitoring of drinking behavior that is compatible with concurrent recording of electrophysiological events. The technique involves transduction of the movement of a water spout induced by tongue contact during licking, to an electrical signal via a coil and magnet. An example of this technique is provided with simultaneous recording of hippocampal EEG in a rat. The advantages of this technique include simplicity of construction, low cost, and insensitivity to most extraneous factors in addition to its compatibility with electrophysiological recording.     

Nuclear domains during muscle atrophy: nuclei lost or paradigm lost?

According to the current paradigm, muscle nuclei serve a certain cytoplasmic domain. To preserve the domain size, it is believed that nuclei are injected from satellite cells fusing to fibres undergoing hypertrophy, and lost by apoptosis during atrophy. Based on single fibre observations in and ex vivo we suggest that nuclear domains are not as constant as is often indicated. Moreover, recent time lapse in vivo imaging of single fibres suggests that at least for the first few weeks, atrophy is not accompanied by any loss of nuclei. Apoptosis is abundant in muscle tissue during atrophy conditions, but in our opinion it has not been unequivocally demonstrated that such nuclei are myonuclei. As we see it, the preponderance of current evidence suggests that disuse atrophy is not accompanied by loss of nuclei, at least not for the first 2 months. Moreover, it has not been proven that myonuclear apoptosis does occur in permanent fibres undergoing atrophy; it seems more likely that it is confined to stromal cells and satellite cells. If muscle atrophy is not related to loss of nuclei, design of intervention therapies should focus on protein metabolism rather than regeneration from stem cells.     

Myopathy associated with chronic alcohol drinking

Summary Muscles of the lower legs of rats given 25% ethanol in water ad libitum for up to 9.5 months were studied using histological, histochemical and electrophysiological techniques. Ethyl alcohol was substituted for about 20% of the total calorific input of the animals. The observations were compared with the structure of the gastrocnemius muscle of five alcoholics with clinical neuropathy. Fibrillation potentials and angulated atrophic fibers were observed in the muscles of animals on alcohol for 9.5 months. No fiber type grouping was present. There was also phagocytosis of the muscle fibers and changes in their internal structure, as reflected by the distribution of NADH-diaphorase. The observed muscle changes in the alcoholics and those in the experimental animals on alcohol differed mainly quantitatively, the only exception being the presence of fiber type grouping in the biopsies from the alcoholics.This study was supported by the Finnish Foundation for Alcohol Studies, Finland     

Licking rate of rats is reduced by intraduodenal and intraportal glucose infusion

The effect of isotonic glucose, urea, and NaCl solutions (0.5 ml) delivered directly to the duodenum or portal system on the rate of drinking a 3.2% glucose or a 3.4% sucrose solution was investigated in rats. Both duodenal and portal glucose infusions produced a decrease in licking rate when the licking test vas administered immediately after the infusion. The effect diminished with increasing time intervals between the infusion and the test. Infusions of urea by both the duodenal and portal routes had effects similar to those produced by glucose but the magnitude of the effect was smaller. Control infusions of isotonic NaCl into the portal vein indicate that the depressing effect of portal glucose and urea on licking rate was chemospecific rather than due to local hypervolemia. Intrajugular infusions of glucose did not alter lick rates, suggesting that the chemoreceptors involved in the effects produced by portal infusions are located in the liver.     

过量酒精致睾丸损伤后的自然修复及其与生精周期的关系

目的探讨大鼠睾丸在过量酒精损伤后的自然恢复及其与生精周期的关系.方法用白酒灌胃制备睾丸毒性损伤模型.停止灌酒1～2个生精周期后检测睾丸的组织学、精子质量及血清性激素的含量.结果酒精使大鼠睾丸有明显的形态学改变,精子质量降低(P＜0.01),性激素水平下降.经过2个生精周期的恢复各项指标有了明显的改善(P＞0.05).结论酒精对睾丸的损伤是可逆性的,但恢复的时间比损伤时所用时间要长.     

Liquid food and tongue activity during sleep and waking in C57Br mice

C57Br/co-Orl mice raised from weaning with a liquid food, were evaluated in terms of the quantitative and qualitative aspects of their vigilance states. The circadian amounts and rhythms of slow wave sleep and paradoxical sleep were not significantly different. The rhythmical activity of the tongue was not found to be modified by the type of food.     

Sensory and motor responses of trigeminal and reticular neurons during ingestive behavior in rats

Summary Activities of 53 neurons in the brain stem were recorded with chronically implanted fine wires in freely eating and drinking rats. Twenty units were isolated from the trigeminal mesencephalic nucleus; 18 were spindle afferents and 2 periodontal afferents. The spindle units were classified into 4 types: 5 units showed rhythmical activity related only to the jaw opening phase during both licking and chewing, 8 units discharged at jaw opening phase during licking, but both at jaw opening and jaw closing phases during eating, 2 units increased phasic activity at jaw opening phase during licking, but increased tonically independent of jaw movements during eating, and the remaining 3 units responded only at jaw closing phase both in licking and eating behavior. Nine units were assumed to be alpha motoneurons isolated from the trigeminal motor nucleus; 2 innervating the temporalis muscle, 3 the masseter muscle, 2 the digastric muscle, and the remaining 2 presumably the pterygoid muscles. These units, with a mean tonic spontaneous rate of about 10 impulses/ s, showed phase-related rhythmical burst activities during licking and eating. Four units were isolated from the trigeminal main sensory nucleus. Sixteen units were isolated from the medullary reticular formation and 1 from the pontine reticular formation. Of these 16 units, 3 from the parvocellular part of the medullary reticular formation were presumably premotor interneurons, and 3 units in the intertrigeminal region, 2 units in the juxtatrigeminal region, and 8 units in the supratrigeminal region were responsive to multiple sensory modalities. These results demonstrate that almost all the units sampled showed characteristic rhythmic activities associated with the position of the tongue or mandible during rhythmical jaw movements.     

液体活检在肿瘤监测管理中的应用

目前临床在诊疗过程中,无活检组织样本的情况下,常规使用液体活检检测肿瘤敏感靶点以寻找敏感靶向药。而最新研究中液体活检计算的肿瘤突变负荷（bTMB）可以对PD-1/L1抑制剂进行疗效预测;同时越来越多的研究发现液体活检可以通过对肿瘤分子负荷进行检测分析,用于肿瘤的预后评估,微小残留病灶监测,以及肿瘤的克隆进化分析,这使得液体活检有望在肿瘤诊疗过程中辅助临床进行更全面的监测管理,本文就此做一综述。     

Effects of pre-exercise ingestion of carbohydrate on glycaemic and insulinaemic responses during subsequent exercise at differing intensities

The development of rebound hypoglycaemia has been reported after pre-exercise carbohydrate (CHO) ingestion in some studies but not in others. Differences in the experimental design and factors such as the exercise intensity are likely to be responsible for the discrepancies between these studies. Exercise intensity might be a crucial factor since it affects both insulinaemia and glucose uptake. Therefore the aim of the present study was to compare the glycaemic and insulinaemic responses to exercise at different intensities after ingestion of a standardized pre-exercise CHO load. Eight moderately trained subjects consumed 75 g of glucose 45 min prior to 20 min of exercise at 40%, 65% or 80% maximal power output. Blood samples were collected before glucose ingestion, at 15 min intervals at rest and 5 min intervals during exercise. During exercise, measurements of heart rate and breath-by-breath analysis of expired gas were performed continuously. The trials were performed at [mean (SEM)] 55 (1), 77 (1) and 90 (1) percentages maximal oxygen uptake . At the onset of exercise, plasma glucose concentration returned to pre-ingestion levels, while the insulin concentration was more than three times higher than at rest [on average 57 (7) compared to 16 (1) μU·ml^–1). During exercise, plasma glucose concentrations decreased during the first 5 min of exercise and then stabilized in all trials at concentrations that would not be considered to be hypoglycaemic. There were no significant differences in glucose or insulin concentrations between the three trials during exercise. These data suggest that the glycaemic response to ingestion of 75 g of CHO 45 min pre-exercise is similar during exercise of different intensities. Electronic Publication     

Lick triggered intracranial stimulation interferes with retrieval of conditioned taste aversion

The effect of brain stimulation on retrieval of conditioned taste aversion (CTA) to 0.15 M LiCl was investigated in 15 overtrained rats. The photoelecttrically detected licks at two drinking spouts delivering water or salt solutions, respectively, were used to trigger single electrical pulses, applied through implanted electrodes to basolateral amygdala or lateral hypothalamus. Current intensities not interfering with licking increased the number of licks required for recognition of the aversive fluid after spout switching from 1 or 2 to more than 5 and occasionally blocked gustatory discrimination completely. Discrimination was disrupted both by amygdalar and lateral hypothalamic stimulation of the same intensity, but amygdalar stimulation was more effective: interference was obtained from all amygdalar (n=21) but from only half of hypothalamic (n=17) stimulation points. The disruptive effects were cumulative. They were almost independent of the lick stimulus delay (1 to 100 ms) and often outlasted the period of stimulation for several min. The interfering effects of electrical stimulation are in accordance with the results of lesion studies indicating that the amygdala and the lateral hypothalamus participate in CTA retrieval, probably by mediating stimulus recognition and/or interruption of consummatory behavior.     

Effect of glucose on plasma glucagon and free fatty acids during prolonged exercise

Summary The effects of glucose ingestion on the changes in blood glucose, FFA, insulin and glucagon levels induced by a prolonged exercise at about 50% of maximal oxygen uptake were investigated. Healthy volunteers were submitted to the following procedures: 1. a control test at rest consisting of the ingestion of 100 g glucose, 2. an exercise test without, or 3. with ingestion of 100 g of glucose. Exercise without glucose induced a progressive decrease in blood glucose and plasma insulin; plasma glucagon rose significantly from the 60th min onward (+45 pg/ml), the maximal increase being recorded during the 4th h of exercise (+135 pg/ml); plasma FFA rose significantly from the 60th min onward and reached their maximal values during the 4th h of exercise (2177±144 ΜEq/l, m±SE). Exercise with glucose ingestion blunted almost completely the normal insulin response to glucose. Under these conditions, exercise did not increase plasma glucagon before the 210th min; similarly, the exercise-induced increase in plasma FFA was markedly delayed and reduced by about 60%. It is suggested that glucose availability reduces exercise-induced glucagon secretion and, possibly consequently, FFA mobilization. Chercheur Qualifié of the Fonds National Belge de la Recherche Scientifique     

Adjunctive drinking and the pituitary-adrenal response: Effects of prior aversive stimulation (preshock)

Two groups of rats were exposed to an intermittent food schedule which induced polydipsia. One group of rats had previously been exposed to inescapable shock. This group showed reduced amounts of polydipsia, and the polydipsia was ineffective in reducing arousal levels (relative to those of the control group), as indexed by plasma corticosterone levels.     

蓝芩口服液治疗慢性咽炎的临床效果观察

目的 研究蓝芩口服液治疗慢性咽炎的临床效果。方法 选取我院2017年1月~2018年1月收治的128例慢性咽炎患者,采用随机数字表法分为观察组与对照组,各64例,对照组给予慢性咽炎常规治疗,观察组在此基础上口服蓝芩口服液治疗。比较两组的治疗效果、患者临床症状缓解时间及不良反应发生情况。结果 观察组临床治疗总有效率为92.19%,优于对照组的68.75%,差异具有统计学意义（P＜0.05）;观察组患者咽部粘膜干燥、咽部异物感、咽部干痒及咽部疼痛出血改善时间为（4.21±2.13）d、（5.51±1.5     

IV nicotine self-administration in rats using the consummatory operant licking response

Nicotine self-administered by tobacco smoking or chewing is very addictive in humans. Rat models have been developed in which nicotine is self-administered IV by the rats pressing a lever. However the reinforcing value of nicotine is much less in these models than the addictiveness of human tobacco use would indicate. The IV nicotine self-administration operant lever press model does not fully capture important aspects of tobacco use in humans. Conditioned oral consumption actions of smoking or chewing tobacco may play important roles in tobacco addiction. Neural circuitry underlying essential food consummatory responses may facilitate consummatory aspects of tobacco intake. To capture this motor consummatory aspect of tobacco addiction in the rat model of nicotine self-administration, we have developed a method of using a licking response instead of a lever press to self-administer IV nicotine. Sprague-Dawley rats were trained to lick one of two waterspouts for IV nicotine (0.03 mg/kg/infusion). With the licking response rats self-administered stable nicotine levels throughout 24 sessions (45 min each) of testing. The number of total licks/session significantly increased in a linear fashion over that period. The number of licks/infusion was substantial, rising steadily with training to an average of over 100 licks/infusion. Including the consummatory motor act with nicotine self-administration could help better model the compulsive aspects of tobacco addiction in humans.     

Glucose ingestion before and during exercise does not enhance performance of daily repeated endurance exercise

Summary The effect of glucose (Glc) ingestion before and during daily, repeated, prolonged exercise on metabolism and performance was tested. Seven young, healthy males performed cycling exercise in two series, with 1 month interval. Each exercise series consisted of 1 h/day on 3 successive days. On the 3rd day, exercise was continued until exhaustion. The intensity was 73.4 (7.7) % [mean (SD)] of maximal oxygen uptake ( ). Glucose (Glc) or placebo (P) drink was ingested 15 min before the start, and at 15 and 45 min of each daily exercise. The total amount of Glc ingested was 43.1 (4.2) g. During exercise, blood Glc concentrations were significantly higher (P<0.05) when Glc was ingested than when P was ingested [Glc 5.14 (0.32) and P 4.12 (4.17) mmol · 1^–1 at exhaustion]. However, Glc ingestion did not improve performance time to exhaustion [Glc 92.05 (29.55) and P 98.07 (27.33) min]. Free fatty acid concentrations were significantly lower when Glc was ingested than when P was ingested [Glc 0.63 (0.21) and P 1.39 (0.46) mmol · l^–1 at exhaustion]. There were no significant differences in exercise heart rate, , respiratory exchange ratio, blood lactate concentrations or rating of perceived exertion between the conditions nor were there any significant differences in these parameters on different days of exercise. It seems that ingestion of small amounts of Glc does not increase the metabolism of carbohydrate or improve the performance of intensive endurance exercise of poorly trained subjects, even when the exercise is repeated daily.