Limited Daily Access Research Articles

Yabancı Dil Öğretimi Sınıflarında Derlem Kullanımı Eğitimi: Öğretmen Adaylarının Algıları

This study investigated the perceptions of 108 Turkish pre-service EFL teachers (PSTs) at a state university in Turkey regarding integrating corpora into language classrooms after the two-week training conducted. Despite the growing interest in using corpora in EFL contexts, very little research has addressed pre-service EFL teachers' perceptions of corpus use. Following a qualitative research design, multiple data collection tools, such as a background survey, pre- and post-training semi-structured interviews, and reflective logs, were utilized. The findings revealed that the PSTs found corpus use beneficial for teaching vocabulary and grammar and preparing authentic teaching materials despite a few drawbacks, such as providing limited daily access and having too much data to analyze. Their remarks revealed that the PSTs would consult corpora in their future teaching experiences. These findings would be useful for teacher educators and teachers who favor using corpora to enrich language learning experiences.

Incidence, risk factors, and therapeutic management of equine colic in Lamongan, Indonesia.

Colic is among the common health issues in equine health management. Gastrointestinal (GI) disorders are the most frequent causes of colic, but dysfunction of other organs and systems inside the abdominal cavity may also contribute. Therefore, it is crucial to identify risk factors for colic of specific etiologies. This study aimed to examine the incidence, risk factors, and best therapeutic management practices for horses with colic. A cohort of 256 horses living in Lamongan, East Java, Indonesia, was randomly recruited based on reports of colic symptoms by owners. Diagnosis and treatment were then conducted with the help of owners. Symptom profiles, risk factors, and therapeutic management strategies were analyzed by Chi-square tests. Of 256 horses enrolled, 217 (84%) were diagnosed with colic, of which 172 (79.3%) were cases of spasmodic colic, 33 (15.2%) of impaction colic, and 12 (5.5%) of intestinal obstruction/displacement. Male sex (χ2 = 16.27; p < 0.001), wheat bran feeding (χ2 = 15.49; p < 0.001), concentrate feed intake >5 kg/day (χ2 = 24.95; p < 0.001), no regular anthelmintic drug treatment (χ2 = 67.24; p < 0.001), GI parasite infection (χ2 = 65.11; p < 0.001), recurrent colic (χ2 = 91.09; p < 0.001), poor body condition score (χ2 = 71.81; p < 0.001), limited daily water access (χ2 = 127.92; p < 0.001), and indications of dental disease (χ2 = 9.03; p < 0.001) were identified as risk factors. The most effective therapies were gastric intubation (χ2 = 153.54; p < 0.001), Vitamin B complex injection (χ2 = 32.09; p < 0.001), fluid therapy (χ2 = 42.59; p < 0.001), and non-steroidal anti-inflammatory drug injection (NSAID). Colic is highly prevalent among horses in Lamongan, East Java, Indonesia. Proper diet, workload management, regular access to clean drinking water, and dental care can reduce colic risk. Recommended therapies include NSAID injection without other analgesics or spasmolytics, fluid therapy, Vitamin B complex, and gastric intubation.

On their way to the north: larval performance of Hemigrapsus sanguineus invasive on the European coast—a comparison with the native European population of Carcinus maenas

The Asian shore crab Hemigrapsus sanguineus has become invasive in North Europe and it co-occurs and competes with the native European shore crab Carcinus maenas. Both species develop through a feeding and dispersive larval phase characterised by several zoeal and a settling megalopa stage. Larvae of marine crabs are vulnerable to food limitation and warming has the potential to exacerbate the negative effects of food limitation on survival and growth. We quantified the combined effects of temperature and food limitation on larval performance (survival and growth) of H. sanguineus and we compared our results with those reported on performance of C. maenas larvae, under the same experimental design and methodology. Larvae from four females of H. sanguineus collected on Helgoland (North Sea) were experimentally reared from hatching to megalopa, at four temperatures (range 15–24 °C) and two food conditions (permanent vs. daily limited access to food). Larval survival of H. sanguineus was low at 15 °C and increased with temperature, in contrast to the high survival reported for C. maenas larvae in the range 15–24 °C. Food limitation reduced survival and body mass of H. sanguineus larvae at all temperatures, but without evidence of the exacerbating effect caused by high temperatures and reported for C. maenas. By contrast, high temperature (24 °C) mitigated the negative effect of food limitation on body mass on H. sanguineus larvae. Advantages of H. sanguineus over C. maenas appear especially under the increased temperatures expected from climate change.

Sucrose intake by rats affected by both intraperitoneal oxytocin administration and time of day.

Daily limited access to palatable food or drink at a fixed time is commonly used in rodent models of bingeing. Under these conditions, entrainment may modulate intake patterns. Oxytocin is involved in circadian patterns of intake and, when administered peripherally, reduces sucrose intake. However, oxytocin's effects on intake under limited-access conditions and its potential interaction with entrainment have not been explored. This study examined the role of entrainment on intake patterns, oxytocin's effects on sucrose intakes and locomotor activity and whether oxytocin's effects were mediated by its actions at the oxytocin receptor. Sated rats received daily 1-h access to 10% sucrose solution either at a fixed or varied time of day. Rats received intraperitoneal oxytocin (0mg/kg, 0.3mg/kg, 1mg/kg, 3mg/kg) prior to sucrose access, and spontaneous locomotor activity was assessed in an open-field test. Rats were then pre-treated with an oxytocin receptor antagonist, L368,899, prior to oxytocin before sucrose access. Intake patterns did not differ between fixed- or varied-time presentations; rats consumed more sucrose solution in the middle as opposed to the early-dark phase. Oxytocin dose-dependently reduced sucrose intakes, but also reduced locomotor activity. There was some evidence of partial blockade of oxytocin-induced sucrose intake reductions by L368,899, but the results were unclear. Time of day and oxytocin impact sucrose solution intake under daily limited access in rats and the sedative-like effects of oxytocin should be considered in future studies on oxytocin and food intake.

Nucleus accumbens shell Orexin-1 receptors are not needed for single-bottle limited daily access alcohol intake in C57BL/6 mice.

Excessive, binge drinking is a major contributor to the great harm and cost of alcohol use disorder. We recently showed, using both limited and intermittent-access two-bottle-choice models, that inhibiting nucleus accumbens shell (Shell) orexin-1-receptors (Ox1Rs) reduces alcohol intake in higher-drinking male C57BL/6 mice (Lei etal., 2019). Other studies implicate Ox1Rs, tested systemically, for several higher-drinking models, including the single-bottle, Rhodes Drinking-in-the-Dark paradigm. Here, we report studies examining whether Shell Ox1Rs contribute to alcohol intake in male mice using a single-bottle Limited Daily Access (LDA) drinking model modified from drinking-in-the-dark paradigms (2-h access starting 3h into the dark cycle, 5 days per week). In addition, some previous work has suggested possible differences in circuitry for one- versus two-choice behaviors, and thus other mice first drank under a single-bottle schedule, and then an additional water bottle was included 2 days a week starting in week 3. Surprisingly, at the same time we were determining Ox1R importance for two-bottle-choice models, parallel studies found that inhibiting Shell Ox1Rs had no impact on drinking using the single-bottle LDA model, or when a second bottle containing water was added later during drinking. Furthermore, we have related Shell Ox1R regulation of intake to basal consumption, but no such pattern was observed with single-bottle LDA drinking. Thus, unlike our previous work showing the importance of Shell Ox1Rs for male alcohol drinking under several two-bottle-choice models, Shell Ox1Rs were not required under a single-bottle paradigm, even if a second water-containing bottle was later added. These results raise the speculations that different mechanisms could promote intake under single- versus two-bottle access conditions, and that the conditions under which an animal learns to drink can impact circuitry driving future intake.

Differential Effects of Continuous versus Intermittent Dietary Fat Intake on Markers of Serotonin Signaling in the Circumvallate Papillae of the Tongue

Taste is a primary sensory modality that guides organisms in their determination of food preferences. Previous studies suggest that orosensory fat sensing may contribute to the intake and preference of dietary fat leading to the development of obesity. CD36 is the proposed fat taste receptor on the circumvallate papillae (CV) of the tongue and mediates fat sensing. Fat signaling via CD36 on the CV involves the regulation of serotonin (5‐HT) in taste receptor cells and activation of gustatory afferent nerves. The aim of these experiments was to investigate the effects of dietary fat intake on 5‐HT signaling in the CV using two feeding paradigms: continuous access to high fat diet (HFD) vs. limited access to dietary fat. We hypothesized that consumption of dietary fat, in specific patterns, contributes to the decreased sensitivity (i.e. hyposensitivity) of fat sensing through 5‐HT signaling dysregulation. The first experiment investigated the effects of continuous access to either a HFD or a low fat diet (LFD) for 1, 3 or 14 days on 5‐HT signaling in the CV. The second experiment investigated the effects of limited daily and intermittent access to dietary fat on 5‐HT signaling in the CV. Body weight and kilocalorie intake were assessed. In the CV, expression levels of CD36, 5‐HT1A, SERT, TPH1, and TPH2 mRNA were determined by Real Time PCR. Continuous HFD consumption for 14 days increased CD36, 5‐HT1A and SERT mRNA expression on the CV, suggesting reduced lingual fat sensing via decreased gustatory signaling from taste receptor cells. Limited, daily access to dietary fat increased CD36 and TPH1 mRNA expression on the CV suggesting enhanced lingual fat sensing compared to chow fed controls. Limited, intermittent access to dietary led to an escalation of fat intake without significant alterations in lingual expression of 5‐HT signaling. These data suggest that different patterns of fat consumption differentially affect 5‐HT signaling in the CV and that continuous access to HFD may lead to decreased orosensory fat perception by altering 5‐HT signaling in taste receptors cells.Support or Funding InformationLSUHSC to SDPThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of timing of corn silage supplementation to Holstein dairy cows given limited daily access to pasture: intake and performance

The timing in which supplements are provided in grazing systems can affect dry matter (DM) intake and productive performance. The objective of this study was to evaluate the effect of timing of corn silage supplementation on ingestive behaviour, DM intake, milk yield and composition in grazing dairy cows. In total, 33 Holstein dairy cows in a randomized block design grazed on a second-year mixed grass–legume pasture from 0900 to 1500 h and received 2.7 kg of a commercial supplement at each milking. Paddock sizes were adjusted to provide a daily herbage allowance of 15 kg DM/cow determined at ground level. The three treatments imposed each provided 3.8 kg DM/day of corn silage offered in a single meal at 0800 h (Treatment AM), equally distributed in two meals 0800 and 1700 h (Treatment AM-PM) or a single meal at 1700 h (Treatment PM). The experiment was carried out during the late autumn and early winter period, with 1 week of adaptation and 6 weeks of measurements. There were no differences between treatments in milk yield, but 4% fat-corrected milk yield tended to be greater in AM-PM than in AM cows, which did not differ from PM (23.7, 25.3 and 24.6±0.84 kg/day for AM, AM-PM and PM, respectively). Fat percentage and yield were greater for AM-PM than for AM cows and intermediate for PM cows (3.89 v. 3.66±0.072% and 1.00 v. 0.92±0.035 kg/day, respectively). Offering corn silage in two meals had an effect on herbage DM intake which was greater for AM-PM than AM cows and was intermediate in PM cows (8.5, 11.0 and 10.3±0.68 kg/day for AM, AM-PM and PM, respectively). During the 6-h period at pasture, the overall proportion of observations on which cows were grazing tended to be different between treatments and a clear grazing pattern along the grazing session (1-h observation period) was identified. During the time at pasture, the proportion of observations during which cows ruminated was positively correlated with the DM intake of corn silage immediately before turn out to pasture. The treatment effects on herbage DM intake did not sufficiently explain differences in productive performance. This suggests that the timing of the corn silage supplementation affected rumen kinetics and likewise the appearance of hunger and satiety signals as indicated by observed changes in temporal patterns of grazing and ruminating activities.

Ability of palatable food consumption to buffer against the short- and long-term behavioral consequences of social defeat exposure during juvenility in rats

In adult rats, access to a palatable diet can buffer against the effects of stressors. Approximately 10% of all adolescents are repeatedly victimized by their peers raising the possibility that palatable food consumption may be relevant to this developmental window. This study assessed the long-term impact of juvenile social defeat exposure on anxiety and depressive-like behavior and whether daily limited access to a palatable diet moderated these behavioral consequences. We also investigated the impact of the palatable diet on behavior during the defeat sessions. Juvenile rats were exposed to either a different adult resident rat (Stress) or handling (Control) from postnatal day (PD) 28–34. All rats had ad libitum access to either chow alone or both chow and limited access (4h/day) to palatable food commencing on PD 21. Results showed that during the defeat sessions, juvenile rats with access to the palatable diet spent less time in submissive postures and displayed significantly longer latencies to submit to the resident. In adulthood, previous exposure to juvenile social defeat resulted in a mild anxiogenic profile in the open field among rats with access to Chow only. Furthermore, defeated rats, regardless of diet, displayed reduced locomotor activity and increased social interaction as adults. These findings suggested only minimal enduring negative consequences from juvenile social defeat exposure which made it challenging to assess potential stress-buffering effects of the palatable diet. This was not the case during the defeat sessions where previous exposure to palatable food appeared protective against the acute stressor effects.

Impaired fear extinction retention and increased anxiety-like behaviours induced by limited daily access to a high-fat/high-sugar diet in male rats: Implications for diet-induced prefrontal cortex dysregulation

Anxiety disorders and obesity are both common in youth and young adults. Despite increasing evidence that over-consumption of palatable high-fat/high-sugar “junk” foods leads to adverse neurocognitive outcomes, little is known about the effects of palatable diets on emotional memories and fear regulation. In the present experiments we examined the effects of daily 2h consumption of a high-fat/high-sugar (HFHS) food across adolescence on fear inhibition and anxiety-like behaviour in young adult rats. Rats exposed to the HFHS diet exhibited impaired retention of fear extinction and increased anxiety-like behaviour in an emergence test compared to rats fed a standard diet. The HFHS-fed rats displayed diet-induced changes in prefrontal cortex (PFC) function which were detected by altered expression of GABAergic parvalbumin-expressing inhibitory interneurons and the stable transcription factor ΔFosB which accumulates in the PFC in response to chronic stimuli. Immunohistochemical analyses of the medial PFC revealed that animals fed the HFHS diet had fewer parvalbumin-expressing cells and increased levels of FosB/ΔFosB expression in the infralimbic cortex, a region implicated in the consolidation of fear extinction. There was a trend towards increased IBA-1 immunoreactivity, a marker of microglial activation, in the infralimbic cortex after HFHS diet exposure but expression of the extracellular glycoprotein reelin was unaffected. These findings demonstrate that a HFHS diet during adolescence is associated with reductions of prefrontal parvalbumin neurons and impaired fear inhibition in adulthood. Adverse effects of HFHS diets on the mechanisms of fear regulation may precipitate a vulnerability in obese individuals to the development of anxiety disorders.

A single alcohol drinking session is sufficient to enable subsequent aversion-resistant consumption in mice.

Addiction is mediated in large part by pathological motivation for rewarding, addictive substances, and alcohol-use disorders (AUDs) continue to extract a very high physical and economic toll on society. Compulsive alcohol drinking, where intake continues despite negative consequences, is considered a particular obstacle during treatment of AUDs. Aversion-resistant drives for alcohol have been modeled in rodents, where animals continue to consume even when alcohol is adulterated with the bitter tastant quinine, or is paired with another aversive consequence. Here, we describe a two-bottle choice paradigm where C57BL/6 mice first had 24-h access to 15% alcohol or water. Afterward, they drank quinine-free alcohol (alcohol-only) or alcohol with quinine (100μM), in a limited daily access (LDA) two-bottle-choice paradigm (2h/day, 5 days/week, starting 3h into the dark cycle), and achieved nearly binge-level blood alcohol concentrations. Interestingly, a single, initial 24-h experience with alcohol-only enhanced subsequent quinine-resistant drinking. In contrast, mice that drank alcohol-quinine in the 24-h session showed significantly reduced alcohol-quinine intake and preference during the subsequent LDA sessions, relative to mice that drank alcohol-only in the initial 24-h session and alcohol-quinine in LDA sessions. Thus, mice could find the concentration of quinine we used aversive, but were able to disregard the quinine after a single alcohol-only drinking session. Finally, mice had low intake and preference for quinine in water, both before and after weeks of alcohol-drinking sessions, suggesting that quinine resistance was not a consequence of increased quinine preference after weeks of drinking of alcohol-quinine. Together, we demonstrate that a single alcohol-only session was sufficient to enable subsequent aversion-resistant consumption in C57BL/6 mice, which did not reflect changes in quinine taste palatability. Given the rapid development of quinine-resistant alcohol drinking patterns, this model provides a simple, quick, and robust method for uncovering the mechanisms that promote aversion-resistant consumption.

Survival and development of larvae of two decapod crustaceans under limited access to prey across a thermal range

We evaluate the potential for decapod larvae to develop under temporally limited daily access to food across a broad thermal range. Larvae of the European lobster Homarus gammarus and velvet swimming crab Necora puber were successfully reared to juvenile and megalopa stages, respectively, at four temperatures (range 15–24°C) under both permanent (24 h) and limited (4 h) daily access to prey. Survival was high in both species with no consistent effect of food limitation. Larvae developed faster with increasing temperature. Model selection indicated that limited access to food in N. puber slowed development from zoea III onwards by 10–25% depending on stage and temperature. Food limitation slowed development of H. gammarus in zoea III and stage IV by 6–30%, with significant interactions of food × temperature. Dry mass, carbon and nitrogen content of H. gammarus all decreased with temperature and were lower under limited access to food. Decapod larvae of the tested species show a high potential to survive and develop with a temporally patchy food resource, although a longer development and smaller body mass at the time of settlement may lead to fitness costs.

Modulation of α5 subunit-containing GABAA receptors alters alcohol drinking by rhesus monkeys.

Alcohol's ability to potentiate the activity of γ-aminobutyric acid (GABA) at GABAA receptors has been implicated as a key mechanism underlying the behavioral effects of alcohol. The complex molecular biology of these receptors raises the possibility that particular receptor subtypes may play unique roles in alcohol's abuse-related effects and that subtype-selective ligands with therapeutic specificity against alcohol might be developed. This study evaluated the capacity of α5GABAA receptor ligands to alter selectively the reinforcing effects of alcohol. Two groups of rhesus monkeys were trained to orally self-administer alcohol or sucrose under fixed-ratio schedules and limited daily access conditions. In addition, following daily self-administration sessions, the behavior of each monkey was scored for both species-typical and drug-induced behaviors. Concentrations of 1 to 6% alcohol maintained self-administration above water levels, engendered pharmacologically relevant blood alcohol levels ranging from 90 to 160mg/dl, and produced changes in behavior typical of alcohol intoxication. Concentrations of 0.3 to 3% sucrose also reliably maintained self-administration. The α5GABAA receptor agonist QH-ii-066 enhanced and the α5GABAA receptor inverse agonist L-655,708 inhibited alcohol, but not sucrose drinking. The changes in alcohol drinking could be reversed with the α5GABAA receptor antagonist XLi-093. However, L-655,708 increased yawning in both alcohol and sucrose drinkers, possibly indicative of an anxiogenic effect. These findings suggest a prominent and specific role for α5GABAA receptor mechanisms in the reinforcing effects of alcohol. Moreover, these results suggest that α5GABAA receptors may represent a novel pharmacological target for the development of medications to reduce drinking. Of ligands modulating this receptor, α5GABAA receptor inverse agonists may hold the most promise as alcohol pharmacotherapies.

Seasonal variation in the nutritional vulnerability of first-stage larval porcelain crab, Petrolisthes laevigatus (Anomura: Porcellanidae) in southern Chile

In temperate marine environments, meroplanktonic larvae face seasonal variations in temperature and food availability. In a laboratory study conducted under seasonally varying temperature conditions, we evaluated the nutritional vulnerability in different cohorts (August, September, October, November, December, and January) of first-stage larvae of a porcellanid crab, Petrolisthes laevigatus. Besides continuously fed and starved control groups (FC, SC), the experimental treatments comprised: (1) differential periods of initial starvation and subsequent feeding (point-of-no-return, PNR: minimum time of initial starvation preventing recovery after later feeding); (2) initial feeding and subsequent starvation (point-of-reserve-saturation, PRS: minimum time of initial feeding allowing for food-independent development through the rest of the moulting cycle); (3) limited daily access to prey (feeding pulses, 4 and 6 h/day). The development time of FC larvae ranged from 10.6 ± 0.4 days (January) to 21.9 ± 2.6 days (August), without significant variation in mortality among cohorts. Under continuous absence of food (SC), first-stage larvae never survived to the zoea II. Short-term feeding pulses had significantly different effects on development time of different cohorts, but not on survival. The PNR was lowest in larvae produced near the end of spring (November). However, when the PNR was expressed as a percentage of the development time in FC larvae, no significant differences were found among cohorts (relative PNR: 32.8–42.5%). The relative PRS was reached after 60.6–73.5% of the development time in FC larvae. In spite of strong seasonal (presumably temperature-induced) differences in the absolute PNR and PRS values of different cohorts, the relative values were generally similar. This suggests that successive cohorts of early larvae can develop with similar success, unless severe winter conditions or oceanographic fluctuations cause a significant decline in short-term prey availability or plankton productivity. Due to long development duration at low temperatures, the larvae produced in winter and early spring have greater potential for dispersal, favoring a genetic exchange between distant populations and colonization of new habitats. Summer larvae, by contrast, may be more important for maintaining local populations. An index of nutritional vulnerability (NVI = PRS 50/PNR 50) is proposed in this paper to compare larvae with differential developmental times. In most larvae studied so far, the NVI is < 1, indicating some degree of independence of food. In larvae of P. laevigatus an index > 1 reflects a relatively high degree of dependence on planktonic food, especially in winter larvae.

Activation of mesolimbic dopamine neurons during novel and daily limited access to palatable food is blocked by the opioid antagonist LY255582

An analog of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine series (LY255582) exhibits high in vitro binding affinity and antagonist potency for the mu-, delta-, and kappa-opioid receptors. In vivo, LY255582 exhibits potent effects in reducing food intake and body weight in several rodent models of obesity. In the present study, we evaluated the effects of LY255582 to prevent the consumption of a highly palatable (HP) diet (a high-fat/high-carbohydrate diet) both when the food was novel and following daily limited access to the HP diet. Additionally, we examined the effects of consumption of the HP diet and of LY255582 treatment on mesolimbic dopamine (DA) signaling by in vivo microdialysis. Consumption of the HP diet increased extracellular DA levels within the nucleus accumbens (NAc) shell. Increased DA in the NAc shell was not related to the quantity of the HP diet consumed, and the DA response did not habituate following daily scheduled access to the HP diet. Interestingly, treatment with LY255582 inhibited consumption of the HP diet and the HP diet-associated increase in NAc shell DA levels. Moreover, the increased HP diet consumption observed following daily limited access to the HP diet was completely prevented by LY255582 treatment. LY255582 may be a useful tool in understanding the neural mechanisms involved in the reinforcement mechanisms regulating food intake.

Effects of naltrexone, duloxetine, and a corticotropin-releasing factor type 1 receptor antagonist on binge-like alcohol drinking in rats.

A 'binge' is defined by National Institute on Alcohol Abuse and Alcoholism as an excessive pattern of alcohol drinking that produces blood-alcohol levels (BALs) greater than 0.08 g% within a 2-h period and may or may not be associated with dependence. The purpose of this investigation was to explore the effects of several neuropharmacological agents in an animal model in which outbred rats voluntarily and orally self-administer pharmacologically meaningful alcohol doses that produce BALs >or=0.08 g% in daily limited access two-bottle choice and operant drinking sessions. Rats were trained to self-administer either 10% (w/v) alcohol solution sweetened with 'supersac' (3% glucose+0.125% saccharin) or supersac alone versus water in a two-bottle choice or operant situation during 30-min daily sessions. Rats were then injected systemically with multiple doses of duloxetine, naltrexone, and the corticotropin-releasing factor antagonist, MPZP, in Latin-square designs. Alcohol binge drinkers reliably consumed amounts of alcohol sufficient to produce BALs >or=0.08 g%. Duloxetine dose-dependently suppressed two-bottle choice alcohol binge drinking and operant alcohol responding as well as operant supersac responding, but did not affect two-bottle choice supersac drinking. Naltrexone-suppressed alcohol binge drinking at very low doses and suppressed supersac drinking at moderate-to-high doses. MPZP did not affect alcohol or supersac consumption. Different profiles for drugs that suppress binge-like alcohol drinking compared with dependence-induced drinking provide a heuristic foundation for future medications development.

Differential regulation of the expression of Period2 protein in the limbic forebrain and dorsomedial hypothalamus by daily limited access to highly palatable food in food-deprived and free-fed rats

Circadian clock genes are rhythmically expressed in many areas of the brain and body and are thought to underlie most endogenous circadian behaviors and physiological processes. Daily rhythms of clock gene expression throughout the brain and body are normally coordinated by the suprachiasmatic nucleus (SCN), but they are also strongly influenced by daily temporal restrictions of food availability. Here, we studied the effects of a daily restricted presentation of highly palatable complete meal replacement, chocolate Ensure Plus (Ensure) in food-deprived (restricted feeding, RF) and free-fed (restricted treat, RT) rats, on the expression of the clock protein, Period2 (PER2) in regions of the brain involved in motivational and emotional regulation; these include the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), the central nucleus of the amygdala (CEA), the basolateral amygdala (BLA), the dentate gyrus (DG) and the dorsomedial hypothalamus (DMH). RF and RT rats consumed similar amounts of Ensure, but changes in the pattern of PER2 expression were seen only in the RF condition, suggesting that changes in PER2 expression in these regions are triggered by the daily alleviation of a negative metabolic state associated with RF and are independent of the positive incentive properties of the consumed substance, per se. In contrast, the expression of the immediate early gene, Fos, was increased in these regions by both RF and RT schedules, showing that signals concerning the incentive value of the consumed food reach these regions. No changes in either PER2 or Fos expression were observed in the SCN of RF or RT rats. These findings demonstrate that mechanisms leading to changes in the expression of PER2 and those affecting the induction of Fos under RF and RT are, at least in part, dissociable.

Daily limited access to sweetened drink attenuates hypothalamic-pituitary-adrenocortical axis stress responses.

Stress can promote palatable food intake, and consumption of palatable foods may dampen psychological and physiological responses to stress. Here we develop a rat model of daily limited sweetened drink intake to further examine the linkage between consumption of preferred foods and hypothalamic-pituitary-adrenocortical axis responses to acute and chronic stress. Adult male rats with free access to water were given additional twice-daily access to 4 ml sucrose (30%), saccharin (0.1%; a noncaloric sweetener), or water. After 14 d of training, rats readily learned to drink sucrose and saccharin solutions. Half the rats were then given chronic variable stress (CVS) for 14 d immediately after each drink exposure; the remaining rats (nonhandled controls) consumed their appropriate drinking solution at the same time. On the morning after CVS, responses to a novel restraint stress were assessed in all rats. Multiple indices of chronic stress adaptation were effectively altered by CVS. Sucrose consumption decreased the plasma corticosterone response to restraint stress in CVS rats and nonhandled controls; these reductions were less pronounced in rats drinking saccharin. Sucrose or saccharin consumption decreased CRH mRNA expression in the paraventricular nucleus of the hypothalamus. Moreover, sucrose attenuated restraint-induced c-fos mRNA expression in the basolateral amygdala, infralimbic cortex, and claustrum. These data suggest that limited consumption of sweetened drink attenuates hypothalamic-pituitary-adrenocortical axis stress responses, and calories contribute but are not necessary for this effect. Collectively the results support the hypothesis that the intake of palatable substances represents an endogenous mechanism to dampen physiological stress responses.

Restricted access to food, but not sucrose, saccharine, or salt, synchronizes the expression of Period2 protein in the limbic forebrain

Restricted feeding schedules (RF) in which daily access to food is limited to a few hours each day can entrain the rhythms of expression of circadian clock genes in the brain and periphery in rodents. The critical factors mediating the effect of RF on rhythms of clock gene expression are unknown. Previously, we demonstrated that daytime RF shifts the phase of expression of the clock protein, Period2 (PER2) in the oval nucleus of the bed nucleus of the stria terminalis in rats kept on a 12-h light/dark cycle, and restored the rhythm of PER2 expression in rats housed in constant light. We now report that RF also modifies the rhythms of PER2 expression in the central and basolateral nuclei of the amygdala and in the dentate gyrus, such that all three areas become synchronized, peaking 12 h after the time of food presentation. Daily limited access to sucrose or saccharine in freely fed rats or scheduled access to saline in sodium-deprived rats had no effect on these PER2 rhythms. Thus, it would appear that the rhythms of PER2 in limbic forebrain structures are sensitive to signals that arise from the alleviation of a negative metabolic state associated with scheduled feeding and that access to rewarding substances in the absence of food deprivation or metabolic challenges, per se, is not sufficient to alter the rhythms of PER2 expression in these regions.

The transition from controlled to compulsive drug use is associated with a loss of sensitization

Rats provided limited daily access to cocaine (1 h) maintain stable levels of drug self-administration over time while those switched to longer access (6 h or more) exhibit escalating patterns of drug intake. These results are reminiscent of human recreational and compulsive drug-taking behavior, respectively. We found that the brains of cocaine-self-administering rats were also qualitatively different in subjects having experienced 6-h (Coc6h) daily access compared to 1-h (Coc1h) access. Fourteen days after an eight-day protocol of cocaine self-administration, all subjects received one infusion of cocaine. Coc1h animals showed enhanced c-Fos reactivity in dopaminergic mesocorticolimbic brain regions and a sensitized locomotor response to IV cocaine. In contrast, both the neural and behavioral sensitization to cocaine was diminished in Coc6h animals. These data suggest that the transition to escalating patterns of drug use is associated with neuroadaptive changes that counteract those initially associated with controlled stable patterns of drug use.

Chronic opioid exposure produces increased heroin self-administration in rats

The purpose of this study was to determine the significance of chronic opioid exposure on the level of heroin self-administration in the rat. Rats were divided into morphine (M, subcutaneous morphine pellets) and placebo (P, subcutaneous placebo pellets) groups and self-administered several different doses of heroin during daily limited access 1-h sessions and prolonged access 8-h sessions. No effects on heroin self-administration occurred when the rats were implanted with morphine pellets and allowed to self-administer heroin in a limited access paradigm (1-h group). However, rats with morphine pellet implantation showed a rapid escalation (Days 0–3 post-pellet) in heroin self-administration in the more prolonged access group (8 h group) compared to placebo-pelleted animals also with 8-h access. Ultimately, placebo-pelleted 8-h exposed animals showed an escalation in heroin self-administration but this effect was delayed until Days 16–18 post-pellet. These results suggest that passive administration of morphine sufficient to produce and maintain dependence facilitates escalation in heroin intake.