Hr Of Food Deprivation Research Articles

Homeostatic Regulation of Energetic Arousal During Acute Social Isolation: Evidence From the Lab and the Field

Recent evidence suggests that social contact is a basic need governed by a social homeostatic system. Little is known, however, about how conditions of altered social homeostasis affect human psychology and physiology. Here, we investigated the effects of 8 hr of social isolation on psychological and physiological variables and compared this with 8 hr of food deprivation in a lab experiment (N = 30 adult women). Social isolation led to lowered self-reported energetic arousal and heightened fatigue, comparable with food deprivation. To test whether these findings would extend to a real-life setting, we conducted a preregistered field study during a COVID-19 lockdown (N = 87 adults; 47 women). The drop in energetic arousal after social isolation observed in the lab replicated in the field study for participants who lived alone or reported high sociability, suggesting that lowered energy could be part of a homeostatic response to the lack of social contact.

Sigma-1 receptor antagonist, PD144418, selectively reduces female motivation for food during negative energy balance

Sigma-1 (σ1) receptors have been investigated for their involvement in learning, rewarding and motivational processes. PD144418, a σ1 receptor antagonist, has been found to produce a dose-dependent attenuation of locomotor activity induced by cocaine, and by itself, does not suppress basal locomotor activity in mice. Moreover, PD144418 decreases the motivational effort of a food-reinforced behavior in male rats, without altering appetite or food palatability. It remains unknown whether the PD144418 can alter the motivational effort of a food-reinforced behavior in response to altered energy homeostasis, as is the case under 24 -h food deprivation. Additionally, while the previous experiments indicate effects in male rats, there has been no research examining the effects of PD144418, or any other σ1 receptor antagonist, on motivational aspects of feeding in females. The present study examined the effects of PD144418 on motivational aspects of feeding in male and female rats using an operant task under sated or food deprived conditions. Results indicated that when animals are sated, at the highest dose (10 μmol/kg), under a progressive ratio (PR) reinforcement schedule, PD144418 significantly attenuated the breakpoint and the number of active lever responses for sucrose pellets in both males and females. When animals are in a state of energy deficit, as is the case following 24-hr food deprivation, PD144418 does not alter motivationally driven operant responding as measured by the breakpoint in either sex but does alter the number of earned reinforcers responses in females.

Hindbrain A2 noradrenergic neuron adenosine 5'-monophosphate-activated protein kinase activation, upstream kinase/phosphorylase protein expression, and receptivity to hormone and fuel reporters of short-term food deprivation are regulated by estradiol.

Estradiol (E) mitigates acute and postacute adverse effects of 12 hr-food deprivation (FD) on energy balance. Hindbrain 5'-monophosphate-activated protein kinase (AMPK) regulates hyperphagic and hypothalamic metabolic neuropeptide and norepinephrine responses to FD in an E-dependent manner. Energy-state information from AMPK-expressing hindbrain A2 noradrenergic neurons shapes neural responses to metabolic imbalance. Here we investigate the hypothesis that FD causes divergent changes in A2 AMPK activity in E- vs. oil (O)-implanted ovariectomized female rats, alongside dissimilar adjustments in circulating metabolic fuel (glucose, free fatty acids [FFA]) and energy deficit-sensitive hormone (corticosterone, glucagon, leptin) levels. FD decreased blood glucose in oil (O)- but not E-implanted ovariectomized female rats and elevated and reduced glucagon levels in O and E, respectively. FD decreased circulating leptin in O and E, but increased corticosterone and FFA concentrations in E only. Western blot analysis of laser-microdissected A2 neurons showed that glucocorticoid receptor type II and very-long-chain acyl-CoA synthetase 3 protein profiles were amplified in FD/E vs. FD/O. A2 total AMPK protein was elevated without change in activity in FD/O, whereas FD/E exhibited increased AMPK activation along with decreased upstream phosphatase expression. The catecholamine biosynthetic enzyme dopamine-β-hydroxylase (DβH) was increased in FD/O but not FD/E A2 cells. The data show discordance between A2 AMPK activation and glycemic responses to FD; sensor activity was refractory to glucose decrements in FD/O but augmented in FD/E despite stabilized glucose and elevated FFA levels. E-dependent amplification of AMPK activity may reflect adaptive conversion to fatty acid oxidation and/or glucocorticoid stimulation. FD augmentation of A2 DβH protein profiles in FD/O but not FD/E animals suggests that FD may correspondingly regulate NE synthesis vs. metabolism/release in the absence vs. presence of E. Mechanisms underlying translation of E-contingent A2 neuron responses to FD into regulatory signaling remain to be determined. © 2016 Wiley Periodicals, Inc.

Effects of duloxetine in rats trained to discriminate between 22 and 2 hours food deprivation

Duloxetine is a serotonin and norepinephrine reuptake inhibitor used clinically to treat depression and generalized anxiety disorder. We tested the effects of duloxetine in rats trained to discriminate 22 hr food deprivation from 2 hr food deprivation in a two‐lever, operant choice task. After rats acquired the discrimination, subjects were food restricted for 22 hr and administered saline and duloxetine (3.2–17.8 mg/kg, s.c.) before generalization tests. Food intake was measured for 1 hr after generalization tests. Duloxetine (10–17.8 mg/kg) significantly reduced the discriminative stimulus effects of 22 hr deprivation, rates of lever pressing, and food intake induced by 22 hr deprivation. The present findings are consistent with our previous research with sibutramine and offer further evidence that serotonin and norepinephrine are important regulators of both food intake and internal states associated with food deprivation.

Effects of amphetamine in rats trained to discriminate between 22 and 2 hr food deprivation

Amphetamine decreases food intake in several species. Previously Corwin, Woolverton, and Schuster (1990) trained food‐restricted rats to discriminative between food ingested 3 or 22 hr before training sessions. In this procedure, amphetamine did not reliably produce discriminative stimulus effects similar to those of recent food ingestion. We tested the effects of amphetamine in non‐restricted rats trained to discriminate 22 hr food deprivation from 2 hr food deprivation in a two‐lever, operant choice task. After rats acquired the discrimination, subjects were food restricted for 22 hr and administered saline or amphetamine (0.032 to 1.0 mg/kg, i.p.) before generalization tests. Food intake was measured for 1 hr after generalization tests. Amphetamine (0.32 mg/kg) significantly decreased the discriminative stimulus effects of 22 hr deprivation. Larger doses of amphetamine eliminated responding. Food intake was significantly affected by amphetamine (0.32 and 1.0 mg/kg). The findings are consistent with the notion that amphetamine affects feeding stimulated by energy needs, and suggest differences between the two discrimination techniques.

Increased feeding and food hoarding following food deprivation are associated with activation of dopamine and orexin neurons in male Brandt's voles.

Small mammals usually face energetic challenges, such as food shortage, in the field. They have thus evolved species-specific adaptive strategies for survival and reproductive success. In the present study, we examined male Brandt's voles (Lasiopodomys brandtii) for their physiological, behavioral, and neuronal responses to food deprivation (FD) and subsequent re-feeding. Although 48 hr FD induced a decrease in body weight and the resting metabolic rate (RMR), such decreases did not reach statistical significance when compared to the control males that did not experience FD. During the first 2 hr of re-feeding following 48 hr FD, voles showed higher levels of feeding than controls. However, when permitted to hoard food, FD voles showed an increase in food hoarding, rather than feeding, compared to the controls. Further, both feeding and food hoarding induced an increase in neuronal activation, measured by Fos-ir, in a large number of brain areas examined. Interestingly, feeding and food hoarding also induced an increase in the percentage of tyrosine hydroxylase immunoreactive (TH-ir) cells that co-expressed Fos-ir in the ventral tegmental area (VTA), whereas both FD and feeding induced an increase in the percentage of orexin-ir cells that co-expressed Fos-ir in the lateral hypothalamus (LH). Food hoarding also increased orexin-ir/Fos-ir labeling in the LH. Together, our data indicate that food-deprived male Brandt's voles display enhanced feeding or food hoarding dependent upon an environmental setting. In addition, changes in central dopamine and orexin activities in selected brain areas are associated with feeding and hoarding behaviors following FD and subsequent re-feeding.

Effects of exendin in rats trained to discriminate between 22 and 2 hr food deprivation

Previous research had demonstrated that GLP‐1 agonists decrease food intake and energy expenditure. Previously we have found that drugs that alter energy expenditure also alter the discriminative stimulus effects of 22 hr food deprivation in rats. We tested the effects of exendin‐4, a GLP‐1 agonist, in rats trained to discriminate 22 hr food deprivation from 2 hr food deprivation in a two‐lever, operant choice task. After rats acquired the discrimination, subjects were food restricted for 22 hr and administered saline or exendin‐4 (0.1–0.56 mcg/kg, i.p.). Thirty min later, the discriminative stimulus effects were assessed. Exendin‐4 did not alter the discriminative stimulus effects of 22 hr food deprivation. A larger dose (1.0 mcg/kg) eliminated responding and significantly decreased food intake. While exendin‐4 decreases intake and rate of responding, exendin‐4 did not alter the “hunger” discrimination.

Hippocampal lesions impair retention of discriminative responding based on energy state cues.

The present research investigated the hypothesis that the hippocampus is involved with the control of appetitive behavior by interoceptive "hunger" and "satiety" signals. Rats were trained to solve a food deprivation intensity discrimination problem in which stimuli produced by 0-hr and 24-hr food deprivation served as discriminative cues for the delivery of sucrose pellets. For Group 0+, sucrose pellets were delivered at the conclusion of each 4-min session that took place under 0-hr food deprivation, whereas no pellets were delivered during sessions that took place when the rats had been food deprived for 24 hr. Group 24+ received the reverse discriminative contingency (i.e., they received sucrose pellets under 24-hr but not under 0-hr food deprivation). When asymptotic discrimination performance was achieved (indexed by greater incidence of food magazine approach behavior on reinforced compared with nonreinforced sessions), half of the rats in each group received hippocampal lesions, and the remaining rats in each group were designated as sham- or nonlesioned controls. Following recovery from surgery, food deprivation discrimination performance was compared for lesioned and control rats in both Groups 0+ and 24+. Discriminative responding was impaired for rats with hippocampal lesions relative to their controls. This impairment was based largely on elevated responding to nonreinforced food deprivation cues. In addition, hippocampal damage was associated with increased body weight under conditions of ad libitum feeding. The results suggest that the inhibition of appetitive behavior by energy state signals may depend, in part, on the hippocampus.

Effects of cholecystokinin and oxytocin in rats trained to discriminate 22 from 2 hours food deprivation

Cholecystokinin and oxytocin have previously been shown to decrease food intake in rats. We tested the effects of cholecystokinin and oxytocin, in rats trained to discriminate 22 hr food deprivation from 2 hr food deprivation in a two‐lever, operant choice task. After rats acquired the discrimination, subjects were food restricted for 22 hr and administered cholecystokinin(1‐10 µg/kg,i.p.) or oxytocin (0.01‐3.2 mg/kg, i.p.) before generalization tests. Food intake was measured for 1 hr after the generalization test. Cholecystokinin dose‐dependently decreased the discriminative stimulus effects of 22 hr deprivation. Oxytocin did not affect significantly affect the discriminative effects of deprivation, but significantly reduced response rate and food intake. The findings support the notion that CCK affects feeding stimulated by energy needs, whereas oxytocin affects feeding via other mechanisms.

Behavioral characterization of amygdala involvement in mediating intra-accumbens opioid-driven feeding behavior.

The present experiments were conducted to provide a more detailed behavioral analysis of the dissociable roles of the basolateral (BLA) and central nucleus (CeA) of the amygdala in mediating intra-accumbens (Acb) opioid-induced feeding of a high-fat diet. Confirming previous findings, temporary inactivation of the CeA with the GABAA agonist muscimol reduced DAMGO (D-Ala2-NMe-Phe4-Glyol5-enkephalin)-induced and baseline food intake, whereas intra-BLA muscimol selectively blocked only DAMGO-induced food intake, leaving baseline feeding intact. However, although inactivation of the BLA reduced DAMGO-induced food intake to control levels, this treatment led to exaggerated number and duration of food hopper entries after food intake had ended. A subsequent experiment under conditions of limited access to the diet found the identical pattern of behavior following intra-Acb administration of DAMGO, regardless of whether the BLA was inactivated. Last, BLA inactivation was shown to have no influence on feeding driven by a state of negative-energy balance (24-hr food deprivation), demonstrating a specific influence of the BLA on opioid-driven feeding. These findings suggest that BLA mediates palatability-driven feeding and that this influence is particular to the consummatory act of ingestion.

Effects of sibutramine and rimonabant in rats trained to discriminate 22 from 2 hours food deprivation

We tested the effects of sibutramine, a norephinephrine and serotonin reuptake inhibitor, and rimonabant, a CB1 antagonist, in rats trained to discriminate 22 hr food deprivation from 2 hr food deprivation in a two‐lever, operant choice task. After rats acquired the discrimination, subjects were food restricted for 22 hr and administered sibutramine (0.3–10 mg/kg, p.o.) or rimonabant (0.3–10 mg/kg, s.c.). One hour later, the discriminative stimulus effects were assessed. Sibutramine significantly decreased the discriminative stimulus effects of 22 hf deprivation; 3.2 mg/kg reduced the effects of deprivation by 50%. A larger dose eliminated responding and decreased food intake. Rimonabant did not affect the discriminative effects of deprivation, but significantly reduced response rates and decreased food intake. While rimonabant decreases intake and rate of responding it does not alter “hunger” discrimination. Such data support the idea sibutramine affects “hunger‐driven” feeding and that the CB1 receptor is involved in feeding associated with affect/reward, rather than feeding stimulated by energy needs.

Adrenocortical response to stress in fasted and unfasted artificially reared 12‐day‐old rat pups

Recent studies have compared artificially reared (AR) rats with dam-reared rats on behavioral outcomes but, despite the fact that they are deprived of their mothers during the stress hyporesponsive period (SHRP), little is known about the effects of AR on the development of the stress response. In this study, the corticosterone (CORT) response to a stressor (saline injection ip) on postnatal Day 12 was assessed in rat pups that had been either dam-reared (DR) or artificially reared since Day 5. In the preceding 24 hr, half the pups in the DR group were maternally deprived (DEP). To control for the food deprivation consequent to maternal deprivation in these groups, half the pups in the AR groups also underwent 24-hr food deprivation (DEP). In the nondeprived condition AR pups did not differ from DR pups on untreated CORT levels or on levels at 1-hr poststress (i.e., all rats demonstrated low levels of CORT characteristic of the SHRP). In contrast, both maternally deprived DR pups and food-deprived AR pups exhibited increased untreated CORT levels as well as a significant increase at 30-min poststress, but CORT elevations were lower in the AR groups than in the DR groups. Thus, long-term maternal deprivation through artificial rearing in rats does not affect the reduced CORT levels and reduced CORT responsiveness associated with the SHRP; however, if animals are food deprived, then all show increased basal CORT levels and a greater CORT response to stress, although this response is lower in AR groups than in DR groups. These results suggest that rat pups artificially reared with adequate nutrition will still exhibit the SHRP.

Effects of food deprivation and a stressor on head pain.

This study sought to experimentally validate 2 self-reported trigger factors of headaches, namely negative affect (anxiety, depression, and anger) and hunger, and to investigate whether these triggers activated the same or different physiological mechanisms. Students (38 women and 18 men) who had suffered from frequent headaches (migraine or tension type) for 6 months or more were randomly assigned to 4 conditions, which involved manipulating hunger by means of 19 hr of food deprivation and negative affect by means of a stressor (difficult to solve anagrams). The findings were consistent with self-reports that hunger and negative affect can precipitate headaches in individuals who suffer from both migraine and tension-type headaches. The physiological responses to the experimental conditions differed, but the findings were not conclusive with respect to whether the trigger factors operated by means of a common biological pathway.

Interoceptive sensory signals produced by 24-hr food deprivation, pharmacological glucoprivation, and lipoprivation.

The energy antimetabolites 2-deoxy-D-glucose (2-DG) and Na-2-mercaptoacetate (MA) both reliably augment food intake in rats. The present research was designed to assess if they also give rise to interoceptive cues like 24-hr food deprivation. Rats were first trained to discriminate a mild shock based on interoceptive cues arising from 1- and 24-hr food deprivation. They were then tested for generalized control of conditioned responding to interoceptive cues produced by 2-DG, MA, and saline. Results suggest that 2-DG (350 mg/kg) produces interoceptive sensory cues like those following 24-hr food deprivation. Further, no evidence was found to suggest that MA, either alone or in combination with 2-DG (100 mg/kg), produces interoceptive cues like 2-DG or 24-hr food deprivation.

Interoceptive sensory signals produced by 24-hr food deprivation, pharmacological glucoprivation, and lipoprivation.

Interoceptive sensory signals produced by 24-hr food deprivation, pharmacological glucoprivation, and lipoprivation.

Neurological dissociation of gastrointestinal and metabolic contributions to meal size control.

A method was developed to separate gastrointestinal (GI) and metabolic contributions to meal size and applied to intact and chronic decerebrate (CD) rats. The effect of a 10-ml milk diet preload or 24 hr of food deprivation on the consumption of a 0.1-M sucrose solution was compared with intake in a no-deprivation/no-preload condition. In the no-deprivation/no-preload condition, rats were given their normal complement of feedings but had the contents of their stomachs removed via a gastric cannula before the intake test. Compared with the no-deprivation/no-preload condition, intact and CD rats consumed significantly less after the preload, but only intact rats ate more after deprivation. Thus intact rats were sensitive to both GI and metabolic influences on intake, whereas CD rats responded to only the GI manipulation. The experiments showed that GI and metabolic contributions to the deprivation response are mediated by neural structures that are at least partly nonoverlapping. The GI component is likely to be contained within the caudal brainstem. The neural systems required for the response to the metabolic changes accompanying deprivation appear to be more widely distributed.

Potency of food deprivation intensity cues as discriminative stimuli.

Rats were trained to use stimuli arising from 0 and 24 hr without food as discriminative signals for shock. In Experiment 1, one group was shocked under 0-hr food deprivation and not shocked under 24-hr food deprivation. Another group received the reverse contingency. The groups received only 3 training trials under each deprivation level. Learning was revealed in a test phase when greater extinction of freezing was observed under the nonshocked than under the shocked deprivation level for both groups. A similar pattern of results was obtained in Experiment 2 when auditory cues were also relevant throughout training. Furthermore, prior training with food deprivation cues seemed to reduce learning about auditory cues subsequently trained in compound with deprivation stimuli. The results indicate that food deprivation intensity cues can be potent discriminative stimuli. The idea that deprivation cues function as conditioned modulatory stimuli cues is also discussed.

Behavioral and biochemical correlates of chronic administration of quipazine

In Experiment 1 groups of rats received single injections of 1, 3, 10, 20 or 40 mg/kg quipazine, and their total 24-hr food and water intake after a 24-hr deprivation period was recorded; there was a dose-related reduction of both food and water intake. In Experiment 2 a group of 15 rats received 5 mg/kg/day, SC quipazine during 29 days, and a control group received saline injections. During treatment, all animals were exposed to a 24-hr food and water deprivation schedule, alternated with 24 hr of free access. Food and water consumption was measured 2 and 24 hr after drug injection; regional 5-HT concentrations were determined at 1 and 13 treatment days by fluorometric assay. Beginning the first treatment day, food and water intake decreased, but by the 13th day the quipazine group had returned to normal ingestion levels. 5-HT concentrations were increased in cerebellum and cortex in acute conditions, but after 13 days they had decreased in cerebellar samples. In Experiment 3 we found that the effects of quipazine on food and water ingestion were recovered after 14 days of discontinuing chronic drug administration.

Aggression by ovariectomized female rats: Combined testosterone/estrogen implants support the development of hormone-dependent aggression

Female hooded rats were ovariectomized and implanted with a single estrogen-filled and a single testosterone-filled Silastic tube. Control animals were ovariectomized and implanted with empty tubes. The implants produced an estrogen concentration of 30 pg/ml and a testosterone concentration of 0.25 ng/ml, levels close to those found in intact females. Two weeks following surgery, all animals were housed in individual cages, placed on a 23-hr food-deprivation schedule, and adapted to a liquid food. They were then housed in hormone-implant/empty-implant pairs and given a series of 3 restricted-access competition tests and 3 free-access competition tests (1/day). The animals were then paired with new partners and given a second series of restricted-access and free-access competition tests. Ovariectomized females with hormone implants were more successful at maintaining access to the liquid food and more aggressive than their competitors without hormone replacement. The aggression was used to maintain access to food during free-access as well as restricted-access competition. Following the competition tests, animals with hormone implants were significantly more aggressive toward an unfamiliar conspecific than were their cagemates with empty implants. The level of success and aggression by females with testosterone + estrogen implants appears greater than that which occurs with either hormone alone and comparable to that observed in intact females.

Enantiomers of phenylpropanolamine suppress food intake in hyperphagic rats

Phenylpropanolamine (PPA, d,1-norephedrine), available in many over-the-counter nasal decongestants and appetite suppressants, is a racemic mixture of the enantiomers d- and 1-norephedrine. The present study evaluates the effects of the individual PPA enantiomers on a variety of nondrug (food deprivation) and drug-induced hyperphagias (2-deoxyglucose and insulin). Racemic PPA has been shown to significantly suppress food intake in these hyperphagic models. Both 1-norephedrine (5–50 mg/kg) and d-norephedrine (5–150 mg/kg), administered intraperitoneally, significantly suppressed feeding after a 4-hr fast during the dark cycle. During the light period, 1-norephedrine (7.5, 10, 15 mg/kg) and d-norephedrine (75, 100, 150 mg/kg) significantly reduced food intake at the 1-hr and 3-hr time intervals in the 24-hr food deprivation-, insulin- and 2-deoxyglucose-induced hyperphagic models. Only 7.5 mg/kg 1-norephedrine in the insulin-induced hyperphagia at 3 hr failed to significantly suppress feeding. These results indicate that each individual PPA enantiomer possesses the ability to suppress food intake in rats made hyperphagic by various stimuli.