Food-deprived Rats Research Articles

Conditioned-reinforcement tests of schedule-induced drinking

ABSTRACTThe purpose of this experiment was to test the role of food to establish a neutral stimulus as a conditioned reinforcer of licking in the schedule-induced drinking (SID) procedure. Throughout the experiment, one group of food-deprived rats received food-tone pairings and another group received food only, according to a fixed time 30-s schedule. Successive experimental phases tested the effects of food-tone pairings on rates of licking a water tube that produced a drop of water and the same tone that was paired with food, on the resistance to extinction of licking, and on the establishment of a new response (button-pressing) reinforced by the tone. Higher frequencies of licking, greater resistance to extinction of licking and higher rates of button pressing were observed for the rats that received food-tone pairings in comparison with the rats that received food only. The results are interpreted as supporting an account that SID is an operant behaviour reinforced by food.

The antagonism of ghrelin alters the appetitive response to learned cues associated with food

The rapid increase in obesity may be partly mediated by an increase in the exposure to cues for food. Food-paired cues play a role in food procurement and intake under conditions of satiety. The mechanism by which this occurs requires characterization, but may involve ghrelin. This orexigenic peptide alters the response to food-paired conditioned stimuli, and neural responses to food images in reward nuclei. Therefore, we tested whether a ghrelin receptor antagonist alters the influence of food-paired cues on the performance of instrumental responses that earn food and the consumption of food itself using tests of Pavlovian-to-instrumental transfer (PIT) and cue potentiated feeding (CPF), respectively. Food-deprived rats received Pavlovian conditioning where an auditory cue was paired with delivery of sucrose solution followed by instrumental conditioning to lever press for sucrose. Following training, rats were given ad libitum access to chow. On test day, rats were injected with the ghrelin receptor antagonist GHRP-6 [D-Lys3] and then tested for PIT or CPF. Disrupting ghrelin signaling enhanced expression of PIT. In addition, GHRP-6 [D-Lys3] impaired the initiation of feeding behavior in CPF without influencing overall intake of sucrose. Finally, in PIT tested rats, enhanced FOS immunoreactivity was revealed following the antagonist in regions thought to underlie PIT; however, the antagonist had no effect on FOS immunoreactivity in CPF tested rats.

Traveling Companions Add Complexity and Hinder Performance in the Spatial Behavior of Rats.

We sought to uncover the impact of the social environment on the spatial behavior of rats. Food-deprived rats were trained in a spatial task of collecting food items from 16 equispaced objects. Following training, they were tested, first alone and then with a similarly-trained cage-mate. It was found that the presence of another rat substantially altered the rats' spatial behavior. Lone rats collected the food items faster while traveling a shorter distance, reflecting a higher efficiency of task completion. When accompanied by a partner, however, the rats traveled together, visiting the same set of objects in each trip with one of them leading. Whether alone or with a partner, rats continued to revisit the same objects; however, more such revisits occurred with a partner. We argue that revisiting objects is not necessarily an error, since returning to past places is an important aspect of rats’ natural behavior. Revisiting an object following food depletion implies that searching for food was not the main driving force in the rats' spatial behavior. Specifically, despite food deprivation, rats were more attentive to one another than to the food. This could be adaptive, since foraging and feeding in groups is a way of poison avoidance in wild rats. Finally, the addition of a social component added complexity to the environment since the rats organized their spatial behavior in reference to one another in addition to their organization in the physical surrounding. Consequently, when tested with a partner, spatial behavior was less structured, less predictable and more chaotic.

The Effect of L-Ornithine on the Phosphorylation of mTORC1 Downstream Targets in Rat Liver.

A non-protein amino acid, L-ornithine (Orn), has been shown to stimulate the urea cycle and tissue protein synthesis in the liver. The purpose of the current study was to assess whether Orn affects the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) pathway, which is involved in protein synthesis. Primary cultured cells isolated from Wistar rat liver were incubated in an amino acid-free medium, followed by addition of Orn for 3 h. The cell lysate was subjected to immunoblotting to evaluate the phosphorylation of downstream targets of mTORC1, including p70S6K, S6, and 4EBP1. To assess the involvement of mTORC1 for the effect of Orn, the cells were pretreated with the mTOR inhibitor rapamycin before the addition of Orn and the cell lysate was subjected to immunoblotting. We next examined whether the effects of Orn were exerted in vivo. Orn was orally administered to 18 h food-deprived rats, the blood and the livers were collected at 1 and 3 h after administration for immunoblotting. Orn treatment for primary cultured cells for 3 h enhanced the phosphorylation of p70S6K, S6, and 4EBP1. In addition, rapamycin blocked the effects of Orn completely (p70S6K and S6) or partially (4EBP1). The oral administration of Orn to the rat also augmented the phosphorylation of mTORC1 downstream targets notably in S6 at 1 h. Our findings demonstrate that Orn has the potential to induce the phosphorylation of downstream targets of mTORC1 in the rat liver. This may be mediated by the augmentation of mTORC1 activity.

Wheel-running reinforcement in free-feeding and food-deprived rats

Rats experiencing sessions of 30min free access to wheel running were assigned to ad-lib and food-deprived groups, and given additional sessions of free wheel activity. Subsequently, both ad-lib and deprived rats lever pressed for 60s of wheel running on fixed ratio (FR) 1, variable ratio (VR) 3, VR 5, and VR 10 schedules, and on a response-initiated variable interval (VI) 30s schedule. Finally, the ad-lib rats were switched to food deprivation and the food-deprived rats were switched to free food, as rats continued responding on the response-initiated VI 30-s schedule. Wheel running functioned as reinforcement for both ad-lib and food-deprived rats. Food-deprived rats, however, ran faster and had higher overall lever-pressing rates than free-feeding rats. On the VR schedules, wheel-running rates positively correlated with local and overall lever pressing rates for deprived, but not ad-lib rats. On the response-initiated VI 30s schedule, wheel-running rates and lever-pressing rates changed for ad-lib rats switched to food deprivation, but not for food-deprived rats switched to free-feeding. The overall pattern of results suggested different sources of control for wheel running: intrinsic motivation, contingencies of automatic reinforcement, and food-restricted wheel running. An implication is that generalizations about operant responding for wheel running in food-deprived rats may not extend to wheel running and operant responding of free-feeding animals.

Rats show molar sensitivity to different aspects of random-interval-with-linear-feedback-functions and random-ratio schedules.

Three experiments examined the impact of various aspects of reinforcement contingencies on responding maintained by free-operant schedules by food-deprived rats. Experiment 1 demonstrated that random interval (RI) and random-interval-with-positive-response-reinforcer-feedback (RI+) schedules maintained similar rates of responding at a variety of reinforcer frequencies. Experiment 2 demonstrated that a random ratio (RR) schedule maintained higher rates than RI or RI+ schedules, except at high rates of reinforcement, where response rates were similar on all schedules. Experiment 3 again demonstrated that RR schedules produced higher response rates than either RI or RI+ schedules, but modification of the RI+ schedule to prevent ratio strain enhanced response rates relative to an RI schedule. Together these results reveal a pattern of interacting factors in schedule controlled behavior: at high rates of reinforcement, this factor overrides the impact of other controlling factors, but as reinforcement rate decreases the joint impact of interresponse times reinforcement, response-reinforcer feedback functions, and ratio strain are observed.

GABA-Mediated Inactivation of Medial Prefrontal and Agranular Insular Cortex in the Rat: Contrasting Effects on Hunger- and Palatability-Driven Feeding.

A microanalysis of hunger-driven and palatability-driven feeding was carried out after muscimol-mediated inactivation of two frontal regions in rats, the agranular/dysgranular insular cortex (AIC) and the ventromedial prefrontal cortex (vmPFC). Food and water intake, feeding microstructure, and general motor activity were measured under two motivational conditions: food-deprived rats given standard chow or ad libitum-fed rats given a palatable chocolate shake. Muscimol infusions into the AIC diminished intake, total feeding duration, and average feeding bout duration for the palatable-food condition only but failed to alter exploratory-like behavior (ambulation or rearing). In contrast, intra-vmPFC muscimol infusions did not alter the overall intake of chow or chocolate shake. However, these infusions markedly increased mean feeding bout duration for both food types and produced a modest but significant reduction of exploratory-like behavior. The lengthening of feeding-bout duration and reduction in rearing were mimicked by intra-vmPFC blockade of AMPA-type but not NMDA-type glutamate receptors. Neither water consumption nor the microstructure of water drinking was affected by inactivation of either site. These results indicate a regional heterogeneity in frontal control of feeding behavior. Neural processing in AIC supports palatability-driven feeding but is not necessary for intake of a standard food under a food-restriction condition, whereas ventromedial prefrontal cortex, and AMPA signaling therein, modulates the duration of individual feeding bouts regardless of motivational context. Results are discussed in the context of regionally heterogeneous frontal modulation of two distinct components of feeding behavior: reward valuation based upon taste perception (AIC) vs switching between ingestive and non-ingestive (eg, exploratory-like) behavioral repertoires (vmPFC).

Individual differences in anticipatory activity to food rewards predict cue-induced appetitive 50-kHz calls in rats

Reward-related stimuli come to acquire incentive salience through Pavlovian learning and become capable of controlling reward-oriented behaviors. Here, we examined individual differences in anticipatory activity elicited by reward-related cues as indicative of how animals attribute incentive salience to otherwise neutral stimuli. Since adult rats can signal incentive motivation states through ultrasonic vocalizations (USVs) at around 50-kHz, such calls were recorded in food-deprived rats trained to associate cues with food rewards, which were subsequently devalued by satiation. We found that the extent to which animals developed conditioned anticipatory activity to food cues while food deprived determined the level of cue-induced appetitive USVs while sated. Re-exposure to reward cues after a free-testing period reinstated USVs, invigorated reward seeking and consumption, and again, increases in calling occurred only in animals with high levels of cue-induced anticipatory activity. Reward-experienced rats systemically challenged with the catecholamine agonist amphetamine or with the dopamine receptor antagonist flupenthixol showed attenuated responses to these drugs, especially for USVs and in subjects with high levels of cue-induced anticipatory activity. Our results suggest that individuals prone to attribute incentive salience to reward cues showed heightened reward-induced USVs which were reliably expressed over time and persisted despite physiological needs being fulfilled. Also, prone subjects seemed to undergo particular adaptations in their dopaminergic system related with incentive learning. Our findings may have translational relevance in preclinical research modeling compulsive disorders, which may be due to excessive attribution of incentive salience to reward cues, such as overeating, pathological gambling, and drug addiction.

LH and testosterone production are more sensitive to the suppressive effects of food deprivation in prenatally undernourished male rats

Although prenatal undernutrition affects the development of metabolic, physiological, and reproductive functions, it remains unclear whether it also affects physiological responses to undernutrition in adulthood. Therefore, in this study we examined whether prenatal undernutrition alters the sensitivity of the hypothalamic–pituitary–gonadal (HPG) axis to fasting in adult male rats. The offspring of ad libitum fed dams (control) and ∼50% food-restricted (during the late gestational period) dams (IUGR) were sub-divided into ad libitum fed (fed) and 48h food deprivation (FD) groups at 10 weeks of age. In each group, the serum levels of luteinizing hormone (LH), testosterone, and leptin and the hypothalamic mRNA expression levels of gonadotropin-releasing hormone (GnRH) regulatory factors were measured. The serum LH and testosterone levels of the IUGR-fed rats were significantly or tend to be higher than those of the control-fed rats, respectively. The serum LH levels of the IUGR-FD rats were lower than those of the IUGR-fed rats. Similarly, the serum testosterone levels of the IUGR-FD rats tended to be lower than those of the IUGR-fed rats. On the other hand, the serum LH and testosterone levels of the control-fed and control-FD rats did not differ. The serum leptin levels of the IUGR fed rats were higher than those of the control-fed rats. The serum leptin levels of the control-FD and IUGR-FD rats were lower than those of the control-fed and IUGR-fed rats, respectively. The hypothalamic neuropeptide Y (NPY) mRNA levels of the IUGR-FD rats were higher than those of the IUGR-fed rats. Similarly, hypothalamic NPY mRNA levels of control-FD rats were higher than those of the control-fed rats. The hypothalamic kisspeptin, kisspeptin receptor, RFamide-related peptide, GPR147, and OBRb mRNA levels of control fed rats did not differ between control-fed and IUGR-fed rats. Their mRNA levels of the fed and FD rats did not differ in the control or IUGR groups. These results suggested that prenatal undernutrition increased the basal LH and testosterone production, whereas they are easily reduced by food deprivation in male rats. Changes of serum leptin level, but not of hypothalamic reproductive related factors, might be involved in these alterations. However, the precise mechanisms responsible for these effects remain unclear.

Impramine, fluoxetine and clozapine differently affected reactivity to positive and negative stimuli in a model of motivational anhedonia in rats

Anhedonia is a relevant symptom in depression and schizophrenia. Chronic stress exposure induces in rats escape deficit, disrupts the dopaminergic response to palatable food and the competence to acquire sucrose self-administration (SA), thus configuring a possible model of motivational anhedonia. Repeated lithium administration reverts stress effects and brings back to control values the breaking point (BP) score, a measure of reward motivation. In this study, we tested on this model two antidepressants, imipramine and fluoxetine, and two antipsychotics, haloperidol and clozapine. The dopaminergic response to sucrose consumption was studied in non food-deprived rats in terms of dopamine D1 receptor signaling in the nucleus accumbens shell (NAcS). More specifically, we studied the modifications in dopamine and cAMP-regulated phosphoprotein of Mr 32,000 (DARPP-32) phosphorylation pattern following sucrose consumption. Fluoxetine reverted the escape deficit and showed no effects on dopaminergic response and sucrose SA. Imipramine reverted sucrose SA and dopamine response deficit in half of the rats and the escape deficit in all animals. Haloperidol did not affect stress-induced deficits. Clozapine-treated rats recovered the dopaminergic response to sucrose consumption and the competence to acquire sucrose SA, although they still showed the escape deficit, thus confirming that motivation toward reward may be dissociated from that to punishment escape. These results indicate that imipramine or fluoxetine are not endowed with a rapid onset antianhedonic effect. On the other hand, clozapine treatment showed a motivational antianhedonic activity similar to that observed after lithium treatment.

Differential modulation of endogenous cannabinoid CB1 and CB2 receptors in spontaneous and splice variants of ghrelin-induced food intake in conscious rats

ObjectiveDysregulation of the endocannabinoid system can lead to the development of obesity and metabolic disorders. Endogenous endocannabinoids act on two cannabinoid receptor subtypes, type 1 (CB1) and type 2 (CB2), to exert their biological actions. The aim of this study was to determine whether CB1 and CB2 receptors modulate feeding behavior. MethodsWe investigated the different roles of CB1 and CB2 receptors in spontaneous and centrally administered splice variants of ghrelin, O-n-octanoylated ghrelin and des-Gln14-ghrelin, stimulation of food intake in conscious rats. ResultsIntraperitoneal (IP) injection of different doses of selective CB2 receptor antagonist AM-630 (0.3, 1, and 3 mg/kg) enhanced cumulative food intake during the first 12 h with a dome-shaped dose-response relationship in freely fed rats, with the most effective dose being 1 mg/kg. In comparison, the selective CB1 receptor antagonist AM-251 (0.3, 1, and 3 mg/kg, IP) dose-dependently suppressed the cumulative food intake in 16-h food-deprived rats. Centrally administered O-n-octanoylated ghrelin and des-Gln14-ghrelin-induced hyperphagic effects were counteracted dose-dependently by IP AM-251, but not AM-630. ConclusionsWe demonstrated that the endogenous CB2 receptor plays a role in inhibiting food intake in the satiated state, whereas the CB1 receptor promotes food intake in the fasted condition. The induction of feeding by central acyl ghrelin is a CB1 receptor-dependent mechanism. Differentially nibbling CB1 and CB2 receptor subtypes may provide a new avenue to treating eating and metabolic disorders.

Amylin receptor signaling in the nucleus accumbens negatively modulates μ-opioid-driven feeding.

Amylin is a peptide co-secreted with insulin that penetrates into the brain, and produces satiation-like effects via actions in the brainstem, hypothalamus, and mesencephalon. Little is known, however, about the effects of amylin in the nucleus accumbens shell (AcbSh), where a circumscribed zone of intense amylin receptor (AMY-R) binding overlaps reported mappings of a 'hotspot' for μ-opioid receptor (μ-OR) amplification of food reward. Here, the ability of intra-AcbSh AMY-R signaling to modulate μ-OR-driven feeding was explored. Amylin (1-30 ng) was administered with the μ-OR agonist, D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) (0.25 μg), directly into the AcbSh of ad libitum-maintained rats. Amylin dose-dependently reversed DAMGO-induced hyperphagia; 3 ng of amylin reduced DAMGO-mediated feeding by nearly 50%. This dose was, however, completely ineffective at altering DAMGO-induced feeding in the anterior dorsal striatum. Intra-AcbSh amylin alone (3-30 ng) modestly suppressed 10% sucrose intake in ad libitum-maintained rats, and chow in food-deprived rats, but only at the 30-ng dose. This result indicates that reversal of AcbSh DAMGO-induced feeding at a 10-fold lower dose was neither due to malaise nor motoric impairment. Finally, intra-AcbSh infusion of the AMY-R antagonist, AC187 (20 μg), significantly attenuated the ability of prefeeding to suppress DAMGO-induced food intake, with no effects in non-prefed rats. Hence, AMY-R signaling negatively modulates μ-OR-mediated appetitive responses at the level of the AcbSh. The results with AC187 indicate that endogenous AMY-R transmission in the AcbSh curtails opioid function in the postprandial period, suggesting a novel pathway for peripheral-central integration in the control of appetitive motivation and opioid reward.

Single rapamycin administration induces prolonged downward shift in defended body weight in rats.

Manipulation of body weight set point may be an effective weight loss and maintenance strategy as the homeostatic mechanism governing energy balance remains intact even in obese conditions and counters the effort to lose weight. However, how the set point is determined is not well understood. We show that a single injection of rapamycin (RAP), an mTOR inhibitor, is sufficient to shift the set point in rats. Intraperitoneal RAP decreased food intake and daily weight gain for several days, but surprisingly, there was also a long-term reduction in body weight which lasted at least 10 weeks without additional RAP injection. These effects were not due to malaise or glucose intolerance. Two RAP administrations with a two-week interval had additive effects on body weight without desensitization and significantly reduced the white adipose tissue weight. When challenged with food deprivation, vehicle and RAP-treated rats responded with rebound hyperphagia, suggesting that RAP was not inhibiting compensatory responses to weight loss. Instead, RAP animals defended a lower body weight achieved after RAP treatment. Decreased food intake and body weight were also seen with intracerebroventricular injection of RAP, indicating that the RAP effect is at least partially mediated by the brain. In summary, we found a novel effect of RAP that maintains lower body weight by shifting the set point long-term. Thus, RAP and related compounds may be unique tools to investigate the mechanisms by which the defended level of body weight is determined; such compounds may also be used to complement weight loss strategy.

Effect of food deprivation on formalin-induced nociceptive behaviors and β-endorphin and sex hormone concentration in rats.

The present study examined the possible role of endogenous opioidergic system in effect of food deprivation on formalin-induced nociceptive behaviors in male and female rats. Also, we investigated the effect of food deprivation on the plasma level of beta-endorphin and sex hormones. Food was withdrawn 48 h prior to performing the formalin test, but water continued to be available ad libitum. The formalin was injected into hind plantar paw. There is significant difference between male and female control rats during phase 2B. Following 48-h food deprivation, both male and female rats exhibited enhanced nociceptive behavior in response to formalin. Food deprivation for 12 and 24 h increased and for 48 h decreased beta-endorphin level in male and female rats. Food deprivation for 24 h decreased testosterone level in male, while it had no significant effect on female rats and food deprivation for 48 h decreased testosterone level in both sexes. Food deprivation for 24 h increased estradiol level in female and that for 48 h had no significant effect on male and female rats. The present study demonstrates the existence of food deprivation for 48 h causes enhancement of nociception in the formalin test in male and female rats that has correlation with decrease in plasma beta-endorphin and testosterone levels.

Concentration and state dependent reductions in corn oil intakes after glossopharyngeal nerve transections in rats

Previous studies indicate a role for the glossopharyngeal nerve (GL) in the detection of dietary fats. The present experiments examined the effects of bilateral glossopharyngeal nerve transections (GLx) on the intake of low (4.8%), moderate (16%), and full-fat (100%) corn oil in non-deprived, food-deprived, and water-deprived rats. The rats had access to oils, 0.3M sucrose, and water in a gustometer that measured number of licks and latency to the first lick during brief access trials. The behavioral measures were used as indices of the amount consumed and the motivation to ingest, respectively. After baseline intakes had stabilized, the rats received GLx or sham transections (Sham) and were then re-tested. Pre and post-surgery responses were compared to determine the impact of GLx on intake and the motivation to ingest. In non-deprived rats, GLx reduced the intake of 4.8% and 16% oils and decreased the motivation to ingest these oils. In food-deprived rats, GLx prevented increases in the ingestion of 4.8% and 16% oils and in the motivation to ingest these oils. In water-deprived rats, GLx reduced the intake of 100% oil and produced a general decrease in the motivation to consume low, moderate, and full-fat emulsions. These results indicate that GL is partially involved in corn oil intake and suggest an interactive effect of oil concentration with homeostatic state.

Recovery of Long-Term Post-Tetanic Potentiation in Conditions of Food Deprivation

The possibility of restoring decayed long-term potentiation of projections of Schaffer collaterals was studied in food-deprived rats on delivery of small food portions. Food delivery was found to produce partial recovery of the amplitude of the population spike of the first response in paired responses in field CA1. Population spike amplitude for the second response showed complete recovery. Food delivery in the control group of deprived rats without prior induction of potentiation did not change responses in field CA1. Recovery of potentiation in these experiments was linked with a defined level of emotional tension in the animal. In natural conditions, recovery of potentiation may be needed to solve tasks directed to satisfying needs of importance to the animal.

Exposure to a high-fat high-sugar diet causes strong up-regulation of proopiomelanocortin and differentially affects dopamine D1 and D2 receptor gene expression in the brainstem of rats

A strong link between obesity and dopamine (DA) has been established by studies associating body weight status to variants of genes related to DA signalling. Human and animal studies investigating this relationship have so far focused mainly on the role of DA within the mesolimbic pathway. The aim of this study was to investigate potential DA receptor dysregulation in the brainstem, where these receptors play a potential role in meal termination, during high-fat high-sugar diet (HFHS) exposure. Expression of other key genes, including proopiomelanocortin (POMC), was also analyzed. We randomized rats into three groups; ad libitum access to HFHS (n=24), restricted HFHS access (n=10), or controls (chow-fed, n=10). After 5 weeks, brainstem gene expression was investigated by qRT-PCR. We observed an increase in POMC expression in ad libitum HFHS-fed rats compared to chow-fed controls (p<0.05). Further, expression of DA D2 receptor mRNA was down-regulated in the brainstem of the HFHS ad libitum-fed rats (p<0.05), whereas expression of the DA D1 receptor was upregulated (p<0.05) in these animals compared to chow-fed rats. In control experiments, we observed no effect relative to chow-fed controls on DA-receptor or POMC gene expression in the hypothalamus of HFHS diet-exposed rats, or in the brainstem of acutely food deprived rats. The present findings suggest brainstem POMC to be responsive to palatable foods, and that DA dysregulation after access to energy-dense diets occurs not only in striatal regions, but also in the brainstem, which could be relevant for overeating and for the development and maintenance of obesity.

Serotonin 1A, 1B, and 7 receptors of the rat medial nucleus accumbens differentially regulate feeding, water intake, and locomotor activity

Serotonin (5-HT) signaling has been widely implicated in the regulation of feeding behaviors in both humans and animal models. Recently, we reported that co-stimulation of 5-HT1&7 receptors of the anterior medial nucleus accumbens with the drug 5-CT caused a dose-dependent decrease in food intake, water intake, and locomotion in rats (Pratt et al., 2009). The current experiments sought to determine which of three serotonin receptor subtypes (5-HT1A, 5-HT1B, or 5-HT7) might be responsible for these consummatory and locomotor effects. Food-deprived rats were given 2-h access to rat chow after stimulation of nucleus accumbens 5-HT1A, 5-HT1B, or 5-HT7 receptors, or blockade of the 5-HT1A or 5-HT1B receptors. Stimulation of 5-HT1A receptors with 8-OH-DPAT (at 0.0, 2.0, 4.0, and 8.0μg/0.5μl/side) caused a dose-dependent decrease in food and water intake, and reduced rearing behavior but not ambulation. In contrast, rats that received the 5-HT1B agonist CP 93129 (at 0.0, 1.0, 2.0 and 4.0μg/0.5μl/side) showed a significant dose-dependent decrease in water intake only; stimulation of 5-HT7 receptors (AS 19; at 0.0, 1.0, and 5.0μg/0.5μl/side) decreased ambulatory activity but did not affect food or water consumption. Blockade of 5-HT1A or 5-HT1B receptors had no lasting effects on measures of food consumption. These data suggest that the food intake, water intake, and locomotor effects seen after medial nucleus accumbens injections of 5-CT are due to actions on separate serotonin receptor subtypes, and contribute to growing evidence for selective roles of individual serotonin receptors within the nucleus accumbens on motivated behavior.

Hindbrain orexin 1 receptors influence palatable food intake, operant responding for food, and food-conditioned place preference in rats.

Brain orexin 1 receptors (OX1Rs) are involved in food-motivated behavior. Most research has focused on forebrain OX1R populations, but hindbrain OX1Rs affect feeding. We hypothesized that hindbrain OX1Rs affect the reward value of food. We examined the effects of hindbrain OX1R stimulation or blockade on motivation for food, palatable high-fat (HF) food intake, and food-conditioned place preference. Rats trained to lever press for sucrose on a progressive ratio (PR) schedule received fourth intracerebroventricular (icv) injections of vehicle, orexin-A (0.1-1nmol), or the OX1R antagonist SB334867 (10-20nmol) before operant test sessions. Effects of these treatments on HF food intake during daily 1-h tests were assessed with fourth icv and nucleus of the solitary tract (NTS) injections. We conditioned a place preference by pairing HF food with one side of a two-sided chamber and then examined the effect of 20nmol fourth icv SB334867 on the expression of that preference. In ad lib fed rats on the PR schedule, fourth icv orexin-A significantly increased responding and breakpoint relative to the vehicle. In 24-h food-deprived rats, fourth icv SB334867 significantly decreased responding and breakpoint. Orexin-A delivered to the fourth ventricle (0.1nmol) or NTS (0.01nmol) increased HF diet intake. Fourth icv SB334867 did not affect HF food intake, but SB334867 delivered either fourth icv (20nmol) or intra-NTS (5-10nmol) suppressed chow intake. Expression of HF food-conditioned place preference was inhibited by fourth icv SB334867. Hindbrain OX1R activity affects food-motivated operant behavior and may play a role in responding to cues that predict palatable food.

Contextual fear cues inhibit eating in food-deprived male and female rats

Previously we have shown that food-deprived male and female rats inhibit food consumption when presented with a discrete conditioned stimulus that signals danger. Here, in a series of three experiments, we examined whether contextual conditioned stimuli can exert the same effect. Experiment 1 paired a distinct context with footshocks, to examine food intake in food-deprived rats upon re-exposure to the context. Experiment 2 used a discrimination protocol with two alternating contexts; rats were given food in one, and received footshocks in the other. This protocol allowed us to monitor food consumption during training in a context never associated with footshocks, and to evaluate consumption at test in a context that had been previously paired with footshocks. Experiments 1 and 2 compared experimental groups to controls that never received footshocks. Experiment 3 used a within-subjects design to assess the specificity of the inhibition by the contextual cues, separate from any generalized effects due solely to the prior experience of footshocks. Our results demonstrate that similar to discrete cues, contextual cues previously associated with aversive events can inhibit feeding in food-deprived animals. These findings are important for our understanding of environmental contributions to the control of food intake.