Forced Desynchronization of Activity Rhythms in a Model of Chronic Jet Lag in Mice

We studied locomotor activity rhythms of C57/Bl6 mice under a chronic jet lag (CJL) protocol (ChrA(6/2)), which consisted of 6-hour phase advances of the light-dark schedule (LD) every 2 days. Through periodogram analysis, we found 2 components of the activity rhythm: a short-period component (21.01 +/- 0.04 h) that was entrained by the LD schedule and a long-period component (24.68 +/- 0.26 h). We developed a mathematical model comprising 2 coupled circadian oscillators that was tested experimentally with different CJL schedules. Our simulations suggested that under CJL, the system behaves as if it were under a zeitgeber with a period determined by (24 -[phase shift size/days between shifts]). Desynchronization within the system arises according to whether this effective zeitgeber is inside or outside the range of entrainment of the oscillators. In this sense, ChrA(6/2) is interpreted as a (24 - 6/2 = 21 h) zeitgeber, and simulations predicted the behavior of mice under other CJL schedules with an effective 21-hour zeitgeber. Animals studied under an asymmetric T = 21 h zeitgeber (carried out by a 3-hour shortening of every dark phase) showed 2 activity components as observed under ChrA(6/2): an entrained short-period (21.01 +/- 0.03 h) and a long-period component (23.93 +/- 0.31 h). Internal desynchronization was lost when mice were subjected to 9-hour advances every 3 days, a possibility also contemplated by the simulations. Simulations also predicted that desynchronization should be less prevalent under delaying than under advancing CJL. Indeed, most mice subjected to 6-hour delay shifts every 2 days (an effective 27-hour zeitgeber) displayed a single entrained activity component (26.92 +/- 0.11 h). Our results demonstrate that the disruption provoked by CJL schedules is not dependent on the phase-shift magnitude or the frequency of the shifts separately but on the combination of both, through its ratio and additionally on their absolute values. In this study, we present a novel model of forced desynchronization in mice under a specific CJL schedule; in addition, our model provides theoretical tools for the evaluation of circadian disruption under CJL conditions that are currently used in circadian research.

Feeding entrainment of locomotor activity and clock gene expression in Senegalese sole, Solea senegalensis

The present study was conducted to investigate the influence of restricted food access on Solea senegalensis behaviour and daily expression of clock genes in central (diencephalon and optic tectum) and pheripheral (liver) tissues. The Senegalese sole is a marine teleost fish belonging to the Class of Actinopterygii, Order Pleuronectiformes and Family Soleidae. Its geographical distribution in the Mediterranean sea is fairly broad, covering the south and east of the Iberian Peninsula, the North of Africa and Middle East until the coast of Turkey. From a commercial perspective Solea senegalensis has acquired in recent years, a key role in aquacolture industry of the Iberian Peninsula. The Senegalese sole is also acquiring an important relevance in chronobiological studies as the number of published works focused on the sole circadian system has increased in the last few years. The molecular mechanisms underlying sole circadian rhythms has also been explored recently, both in adults and developing sole. Moreover, the consideration of the Pleuronectiformes Order as one of the most evolved teleost groups make the Senegalese sole a species of high interest under a comparative and phylogenetic point of view. All these facts have reinforced the election of Senegalese sole as model species for the present study. The animals were kept under 12L:12D photoperiod conditions and divided into three experimental groups depending on the feeding time: fed at midlight (ML), middark (MD) or random (RND) times. Throughout the experiment, the existence of a daily activity rhythm and it synchronization to the light-dark and feeding cycles was checked. To this end locomotor activity was registred by means of two infrared photocells placed in pvc tube 10 cm below the water surface (upper photocell) and the other one was located 10 cm above the bottom of the tank (bottom photocell). The photocell were connected to a computer so that every time a fish interrupted the infrared light beam, it produced an output signal that was recorded. The number of light beam interruptions was stored every 10 minutes by specialized software for data acquisition.

Responses of the Circadian Locomotor Activity Rhythm of Mus Booduga to Shifts in LD Schedules

The responses of the field mouse Mus booduga to shifts in schedules of LD cycles were monitored and the results were interpreted with the help of a PRC constructed for the same species. The results reveal that, M. booduga reentrained faster with a lesser number of transients after delay shifts than advance shifts, thus exhibiting “asymmetry effect.” A positive correlation was observed between the number of transients and the number of hours of shift. In most of the shifts, the sign of the transients (negative for delaying transients and positive for advancing transients) coincided with the direction of the shift. Interestingly, 11 and 12 h of advance shifting resulted in delaying transients. An 11-h advance shift can also be interpreted as a 13-h delay. Reentrainment through delaying transients is faster as compared to reentrainment through advancing transients. Thus, this animal might have taken a “shorter route,” as proved by the fact that an 11-h advance shift has evoked delaying transients. But a 13-h advance shift evoked only advancing transients. This prompts us to speculate that there may be a “phase jump” in M. booduga. Further, irrespective of whether L or D has been doubled in a 12-h shift, both evoked only delaying transients.

Effects of seasonal change on activity rhythms and swimming behavior of age-0 bluefish (Pomatomus saltatrix) and a description of gliding behavior

Daily and seasonal activity rhythms, swimming speed, and modes of swimming were studied in a school of spring-spawned age-0 bluefish (Pomatomus saltatrix) for nine months in a 121-kL research aquarium. Temperature was lowered from 20° to 15°C, then returned to 20°C to match the seasonal cycle. The fish grew from a mean 198 mm to 320 mm (n= 67). Bluefish swam faster and in a more organized school during day (overall mean 47 cm/s) than at night (31 cm/s). Swimming speed declined in fall as temperature declined and accelerated in spring in response to change in photoperiod. Besides powered swimming, bluefish used a gliding-upswimming mode, which has not been previously described for this species. To glide, a bluefish rolled onto its side, ceased body and tail beating, and coasted diagonally downward. Bluefish glided in all months of the study, usually in the dark, and most intensely in winter. Energy savings while the fish is gliding and upswimming may be as much as 20% of the energy used in powered swimming. Additional savings accrue from increased lift due to the hydrofoil created by the horizontal body orientation and slightly concave shape. Energy-saving swimming would be advantageous during migration and overwintering.

Effect of Co-administration of Morphine and Cholinergic Antagonists on Y-maze Spatial Recognition Memory Retrieval and Locomotor Activity in Mice

吗啡和胆碱能系统的相互作用已在多项研究中提到,本实验想查明吗啡是否能和胆碱能拮抗剂、东莨菪碱以及阿托品共同作用对小鼠的Y迷宫空间识别记忆提取产生影响.采用测试前腹腔给药的方法,选用3种剂量的吗啡(5、1.5、0.5mg/kg),两种剂量的东莨菪碱(1、0.1mg/kg),以及两种剂量的阿托品(0.5、0.1mg/kg),剂量由高到低相配对作为联合给药的手段.其结果表明:1)0.5mg/kg低剂量吗啡与0.1 mg/kg低剂量的东莨菪碱,或与0.1 mg/kg低剂最的阿托品联合给药的小鼠,在记忆提取测试中, 空间探查行为(各臂停留时间百分比)对新异臂没有偏好,而新奇探索行为(各臂访问次数百分比)仍保持了对新异臂的偏好,而相应剂最药物单独给药的小鼠记忆提取均没有被损害;2)吗啡能和东莨菪碱相互作用使小鼠的活动性显著增强.暗示吗啡和胆碱能拮抗剂对小鼠空间记忆提取的破坏存在一定程度的相互作用.

Effect of adrenalectomy and corticosterone replacement on prepulse inhibition and locomotor activity in mice

1 Stress is a risk factor in psychiatric illnesses such as schizophrenia. The aim of the present study was to investigate the effect of different circulating levels of the adrenal steroid corticosterone (CORT) on locomotor hyperactivity and prepulse inhibition of acoustic startle, two behavioural animal models of aspects of schizophrenia. 2 Male C57BL/6J mice (n = 10 per group) were anaesthetised with isoflurane and sham-operated or adrenalectomised (ADX). ADX mice were implanted with 50 mg pellets consisting of 100% cholesterol, or 2, 10 or 50 mg of CORT mixed with cholesterol. CORT pellet implantation dose dependently increased plasma CORT levels 3 weeks after surgery. Starting 1 week after surgery, mice were tested for prepulse inhibition after injection of saline or 5 mg kg(-1) of haloperidol. 3 In intact mice and in mice implanted with 10 mg of CORT, haloperidol treatment significantly increased prepulse inhibition (average values from 38 - 42 to 52%). Similar results were observed when testing the mice for amphetamine-induced locomotor hyperactivity (5 mg kg(-1)). In contrast, there was no significant effect of haloperidol in mice implanted either with cholesterol or 2 or 50 mg of CORT. 4 These results in behavioural animal models of schizophrenia suggest an important role of the stress hormone CORT in modulating dopaminergic activity in this illness.

Locomotor activity rhythm in the Japanese eel Anguilla japonica elvers

Under artificial LD cycles (6, 12, 18 L), the elvers of Japanese eel, Anguilla japonica, showed a 24 h cycle of locomotor activity rhythm being most active at light transitions: the eels' activity rose to a primary peak after lights-off, followed by a quiescent period during which they buried into the shelters or lying motionlessly on sand for most of the time, and then reached a secondary peak before lights-on. Elvers could resynchronize their activity rhythm with a new photo cycle within 4 d. Moreover, their activity level at dark phase significantly increased as the light period was prolonged: higher activity levels during shorter dark period. However, the elvers did not display clearly the existence of a circadian rhythm under constant light or dark conditions. The timing of daily activity rhythm evidenced in the Japanese eels may occur through the action of the LD cycles with a weak participation of an endogenous circadian system. In all the LD cycles, over 99% of the activity occurred in the dark phase, indicating that the eels were always nocturnally active no matter what time of day it might be. Under 12 L conditions, the eels' activity level and the time outside sand were significantly elevated both at light and dark phases as temperature increased from 10 similar to 15 to 20 similar to 25 degrees C. The activity rhythm pattern (i.e., two peaks occurring around light transitions) did not apparently change among temperatures. However, in contrast with the primary activity peaks immediately after lights-off at 20 and 25 degrees C, the timing of the primary peaks at 10 and 15 degrees C showed a latency of a few hours following lights-off, indicating the inhibiting effect of low temperature on the eels' activity.

Environmental modulation of ethanol-induced locomotor activity: Correlation with neuronal activity in distinct brain regions of adolescent and adult Swiss mice

Drug abuse is a concerning health problem in adults and has been recognized as a major problem in adolescents. induction of immediate-early genes (IEG), such as c-Fos or Egr-1, is used to identify brain areas that become activated in response to various stimuli, including addictive drugs. It is known that the environment can alter the response to drugs of abuse. Accordingly, environmental cues may trigger drug-seeking behavior when the drug is repeatedly administered in a given environment. The goal of this study was first to examine for age differences in context-dependent sensitization and then evaluate IEG expression in different brain regions. For this, groups of mice received i.p. ethanol (2.0 g/kg) or saline in the test apparatus, while other groups received the solutions in the home cage, for 15 days. One week after this treatment phase, mice were challenged with ethanol injection. Acutely, ethanol increased both locomotor activity and IEG expression in different brain regions, indistinctly, in adolescent and adult mice. However, adults exhibited a typical context-dependent behavioral sensitization following repeated ethanol treatment, while adolescent mice presented gradually smaller locomotion across treatment, when ethanol was administered in a paired regimen with environment. Conversely, ethanol-treated adolescents expressed context-independent behavioral sensitization. Overall, repeated ethanol administration desensitized IEG expression in both adolescent and adult mice, but this effect was greatest in the nucleus accumbens and prefrontal cortex of adolescents treated in the context-dependent paradigm. These results suggest developmental differences in the sensitivity to the conditioned and unconditioned locomotor effects of ethanol. (C) 2008 Elsevier B.V. All rights reserved.

Repeated administration of caffeine increases femproporex-induced locomotor activity in adolescent and adult rats

Caffeine and femproporex are psychostimulants drugs widely consumed in Brazil. Behavioral sensitization is defined as an augmentation in the behavioral effect of a psychostimulant upon re-administration. Repeated administration of a psychostimulant produces behavioral sensitization to that drug and cross-sensitization to other drugs. We investigated whether repeated administration of caffeine increases femproporex-induced locomotor activity in adolescent and adult rats. Forty-eight adolescent (postnatal day 27) and 32 adult (postnatal day 60) received i.p. injections of caffeine (CAF) (10.0 mg/kg) (adolescent N = 24; adult N = 16)) or saline (adolescent N = 24; adult N = 16) once daily for ten days. Three days following the last injection each group was subdivided and received a challenge injection of femproporex (2.0 mg/kg i.p) or saline. Locomotor activity was recorded for 1 hour in 5 - minute intervals. Our results showed that repeated injections of caffeine increased femproporex - induced locomotor activity in adult and adolescent rats.

Effects of adolescent exposure to cocaine on locomotor activity and extracellular dopamine and glutamate levels in nucleus accumbens of DBA/2J mice

Adolescents differ from adults in their acute sensitivity to several drugs of abuse, but little is known about the long-term neurobehavioral effects of adolescent drug exposure. To explore this further, we evaluated the locomotor responses to repeated cocaine administration in adolescent and adult male DBA/2J mice and alterations in extracellular levels of dopamine (DA) and glutamate (GLU) in the nucleus accumbens (NAc) in response to a subsequent cocaine challenge. Adolescent and adult mice were treated daily with saline or cocaine (10 mg/kg, i.p) for 9 consecutive days. Ten days following the last injection, animals were implanted with microdialysis probes and 24 h later microdialysis samples were collected before and after an acute cocaine challenge. Adolescents but not adults demonstrated development of behavioral sensitization to cocaine. Microdialysis procedures revealed that cocaine-treated mice displayed greater peak increases in extracellular DA in response to a subsequent cocaine challenge as compared to saline-treated mice, in contrast with lower peak increases in extracellular GLU. While adults exhibited greater peaks in extracellular DA in response to cocaine than adolescents did, adolescent mice presented a more rapid onset of peak extracellular DA levels than adults. Our results indicate differences in the behavioral and neurochemical responses to cocaine in adolescent versus adult mice, which may be relevant to the increased risk of developing addiction in humans who are exposed to drugs of abuse during adolescence. (C) 2007 Elsevier B.V. All rights reserved.

Effects of caffeine on locomotor activity of horses: Determination of the no-effect threshold

Caffeine is the legal stimulant consumed most extensively by the human world population and may be found eventually in the urine and/or blood of race horses, the fact that caffeine is in foods led us to determine the highest no-effect dose (HNED) of caffeine on the spontaneous locomotor activity of horses and then to quantify this substance in urine until it disappeared. We built two behavioural stalls equipped with juxtaposed photoelectric sensors that emit infrared beams that divide the stall into nine sectors in a 'tic-tac-toe' fashion. Each time a beam was interrupted by a leg of the horse, a pulse was generated; the pulses were counted at 5-min intervals and stored by a microcomputer. Environmental effects were minimized by installing exhaust fans producing white noise that obscured outside sounds. One-way observation windows prevented the animals from seeing outside. The sensors were turned on 45 min before drug administration (saline control or caffeine), the animals were observed for up to 8 h after i.v. administration of 2.0, 2.5, 3.0 or 5.0 mg caffeine kg(-1). The HNED of caffeine for stimulation of the spontaneous locomotor activity of horses was 2.0 mg kg(-1). The quantification of caffeine in urine and plasma samples was done by gradient HPLC with UV detection. The no-effect threshold should not be greater than 2.0 mug caffeine ml(-1) plasma or 5.0 mug caffeine ml(-1) urine. Copyright (C) 2001 John Wiley & Sons, Ltd.

Effects of chronic stress on nicotine-induced locomotor activity and corticosterone release in adult and adolescent rats

We examined nicotine-induced locomotion and increase in corticosterone plasma levels in adolescent and adult animals exposed to chronic restraint stress. Adolescent [postnatal day (P) 28-37] and adult (P60-67) rats were restrained for 2 hours once daily for 7 days. Three days after the last exposure to stress, the animals were challenged with saline or nicotine (0.4 mg/kg subcutaneously). Nicotine-induced locomotion was recorded in an activity cage. Trunk blood samples were collected in a subset of adolescent and adult rats and plasma corticosterone levels were determined by radioimmunoassay. Exposure to stress did not affect the nicotine-induced locomotor- or corticosterone-activating effects in both ages.

Comparison of caffeine-induced locomotor activity between adolescent and adult rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Development and characterization of an equine behaviour chamber and the effects of amitraz and detomidine on spontaneous locomotor activity

This report describes the development of a behaviour chamber and the validation of the chamber to measure locomotor activity of a horse, Locomotor activity was detected by four Mini-beam sensors and recorded on a data logger every 5 min for 22 h. Horses were more active during daytime than in the evening, which was at least partially related to human activity in their surroundings. To validate the ability of the chambers to detect changes in activity, fentanyl citrate and xylazine HCl, agents well-characterized as a stimulant and a depressant, respectively, were administered to five horses. Fentanyl citrate (0.016 mg/kg) significantly increased locomotor activity which persisted for 30 min, Xylazine HCl (1 mg/kg) significantly reduced locomotor activity for 90 min. Amitraz produced a dose-dependent decrease in locomotor activity, lasting 75 min for the 0.05 mg/kg dose, 120 min for the 0.10 mg/kg dose, and 180 min for the 0.15 mg/kg dose, In a separate experiment, yohimbine administration immediately reversed the sedative effect of amitraz, This suggests there is a similarity in the mode of action of amitraz, xylazine and detomidine, as yohimbine acts primarily by blocking central alpha 2-adrenoceptors that are stimulated by agents like xylazine, There was also a significant decrease in locomotor activity following injection of detomidine (0.02, 0.04 and 0.08 mg/kg) for 1.5, 3.5 and 5.0 h, respectively, the locomotor chamber is a useful, sensitive and highly reproducible tool for measuring spontaneous locomotor activity in the horse, which allows investigators to determine an agent's average time of onset, duration and intensity of effect on movement.