Effects of VMH lesions on schedule induced and schedule dependent behaviors

Ten male hooded rats were exposed to an FI 1 min food reinforcement generator schedule at 80% body weight and schedule dependent lever pressing and schedule induced licking and drinking were recorded. When lever pressing, licking, and drinking stabilized the 10 rats were divided into two groups. One group was composed of 4 animals subjected to sham lesion procedures plus one animal with asymmetrical ventromedial hypothalamic (VMH) lesions. The other group was composed of 5 animals with bilateral symmetrical VMH destruction. Results demonstrate that VMH destruction produces a slight transient decrease only in water intake when on schedule at 80% body weight. When animals are returned to ad lib eating and body weight increased and they are returned to the test chamber, the VMH lesion animals display increased licking and drinking. Although VMH lesion animals ate and drank more than controls, they did not eat more in response to food deprivation and did not drink more in response to water deprivation and the intraperitoneal administration of hypertonic saline. The presence or absence of food or water was the determining factor in the overeating or excessive drinking of the VMH lesion animals. Results are discussed in terms of gastrointestinal influences on the hypothalamic mechanisms involved in the production of schedule induced behaviors.     

Effects of lateral hypothalamic lesions on schedule dependent and schedule induced behavior

Rats were reduced to 80 percent body weight and were exposed to an FI 1 min food reinforcement schedule for 30 min daily until lever presses, licks and water consumption stabilized for at least 10 days. Six animals were subjected to bilateral mid lateral hypothalamic (LH) lesions and 6 animals to bilateral posterior LH lesions. Animals were tested for 50 days following the lesions at 80 percent body weight, were permitted to recover body weight, and were tested for an additional 30 days under ad lib feeding and after body weight recovered. Animals were then subjected to the following four home cage tests: food consumption following food deprivation; drinking following water deprivation; insulin induced eating; and salt arousal of drinking. On the basis of the data collected in these tests and lesion locus and size, the 12 experimental animals were divided into 3 groups--asymmetrical, typical and posterior bilateral LH lesion and were compared to a sham lesion control group of 4 animals. The asymmetrical LH lesion group was similar to the sham lesion group except lever pressing was significantly depressed. Typical bilateral lesion animals displayed the usual LH syndrome with prolonged depression of both schedule dependent lever pressing and schedule induced licking and drinking. Posterior bilateral LH lesions produced the most drastic effects on both schedule dependent and schedule induced behavior. Results indicate that the neural mechanism which is involved in schedule induced polydipsia is destroyed by posterior bilateral LH lesions.     

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

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

Schedule dependent and schedule induced behavior at reduced and recovered body weight.

Rats maintained at 80 percent ad lib feeding body weight became hyperdipsic during 60 min FI-1 min food reinforcement sessions in standard rat operant test chambers. Animals were then allowed to return gradually to their ad lib feeding weight and were tested again in the same experimental chambers for 18 daily and 9 weekly sessions. Data were obtained for test sessions of 10, 30 and 60 min. When body weight recovered, schedule dependent lever pressing and eating as well as schedule induced licking and drinking occurred at reduced frequencies. The behavior endured throughout the test session and over periods as long as 80 days. These persistent and robust stereotyped behaviors are evoked by specific environmental stimuli during a resultant increased responsiveness.     

Effects of basolateral amygdaloid lesions on schedule induced and schedule dependent behavior.

Rats were reduced to 80% body weight and were exposed to an FI-1 min food reinforcement schedule for 30 min daily until lever presses, licks, and water consumption stabilized for at least 10 days. Bilateral lesions were then made in the basolateral amygdala of all animals. Animals were tested for 40 days following the lesions at 80% body weight, were permitted to recover body weight by increasing food rations, and were tested for an additional 15 days under ad lib feeding. Animals were then subjected to the following tests: food consumption following food deprivation, drinking following water deprivation, and salt arousal of drinking. In addition, consumption of 6.85% sucrose, 25% sucrose, 8% glucose, 21% glucose, and 0.125% Na saccharin on a FI-1 min food reinforcement schedule and under home cage conditions were measured. On the basis of these data and lesion locus the 8 animals were divided into 2 groups, bilaterally symmetrical experimentals and asymmetrical controls. Although no effects were observed in licking, water consumption, and lever pressing, animals with bilateral symmetrical lesions of the basolateral amygdala displayed relatively permanent deficits in their responses to various taste stimuli. The effects of these lesions are evaluated and discussed in terms of the lateral hypothalamic involvement in schedule induced and schedule dependent behavior.     

Effects of 2-deoxy-D-glucose on schedule dependent and schedule induced behavior and ingestion at different body weights.

The effects of intraperitoneally administered 2-deoxy-D-glucose (2DG) at 0, 50, 150, 300 and 600 mg/kg, were studied in four experiments. Experiments 1 and 2 determined the effects of 2DG on schedule induced licking and drinking and schedule dependent lever pressing in rats maintained at 80% and ad lib free feeding body weights during 3 hr on an FI-1 min food reinforcement schedule. Experiments 3 and 4 evaluated the effects of 2DG on free access home cage food and water consumption under the same body weight conditions. Decreases in food and water consumption were observed under both feeding conditions when animals were reduced to 80% free feeding body weight. At ad lib feeding body weight, 2DG administration had no effects on licking, drinking, and lever pressing during FI-1 min scheduled food reinforcement or on free access home cage feeding and drinking. The effects of 2DG on ingestive behavior are discussed in terms of central and peripheral glucosensitive cells and the consequences of blocking glucose utilization at different body weights under different stimulus conditions.     

Effects of thalamic taste nuclei lesions on the ingestion of sapid solutions and schedule induced and schedule dependent behavior

Rats were reduced to 80 percent body weight and were exposed to an FI-1 min food reinforcement schedule for 30 min daily until lever presses, licks, and water consumption stabilized for at least 10 days. Bilateral lesions were then made in the thalamic taste nucleus of all animals. Animals were tested for 50 days following the lesions at 80 percent body weight, were permitted to recover body weight by increasing food rations, and were tested for an additional 30 days under ad lib feeding. Animals were then subjected to the following tests: food consumption following food deprivation, drinking following water deprivation, salt arousal of drinking, and drinking of 7°C water following water deprivation. In addition, consumption of 6.85% sucrose, 25% sucrose, 8% glucose, 21% glucose, and 0.125% Na saccharin on a FI-1 min food reinforcement schedule and under home cage conditions were measured. On the basis of these data and lesion locus the 8 animals were divided into 2 groups, bilaterally symmetrical experimentals and asymmetrical controls. Although only transient effects were observed in licking, water consumption, and lever pressing, animals with bilateral symmetrical lesions of the medial ventral thalamic nuclei displayed relatively permanent deficits in their responses to various taste stimuli and the salt arousal of drinking. The effects of these lesions are evaluated and discussed in terms of the lateral hypothalamic invovlement in schedule induced and schedule dependent behavior.     

Schedule dependence of schedule induced polydipsia and lever pressing

Two male hooded rats maintained at 80% of initial body weight were tested for schedule induced polydipsia at fixed time (FT) intervals of 1.0, 2.0, 3.0, 4.0 and 5.0 min. A total of 180 45 mg pellets were delivered during the test session. Each animal was tested five times at each FT interval. Total number of licks, lever presses and water consumption increased as the FT interval was increased to a maximum at 4.0 min and then decreased at 5.0 min. Although delivery of the food pellet was not contingent upon pressing the lever, lever pressing occurred and followed the same time related function as licking and water consumption. Results were interpreted in terms of increased motor activity attributed to intermittent food delivery.     

Adjunctive behavior in humans on a food delivery schedule

Adjunctive behavior as indexed by increased activity has been shown previously in adult humans who were performing cognitive tasks or playing games of chance on a fixed interval schedule. In the present experiment with eating as the schedule controlled behavior, the amount of movement unrelated to eating was measured for eight subjects under three conditions. Movement scores were significantly higher when food was available either ad lib or on a FI 60 food delivery schedule than when food was not available. Data showed that with ad lib food, subjects operated on a self imposed schedule. These results establish the first direct comparison between animal and human adjunctive behaviors.     

Clonidine suppression and its adrenoreceptor mediation in schedule-induced polydipsia

Rats were trained in a fixed-interval, one-minute (FI 1 min) food reinforcement schedule for 1 hour daily at reduced body weight until their lever presses, licks and water intake all became stabilized for 6 days. Two experiments were performed to examine the function of sympathetic activity in schedule-induced polydipsia. In experiment 1, intracerebroventricular injection of clonidine (0.75-37.5 nmol) produced a dose-related suppression of schedule-induced drinking and licking and schedule-dependent lever pressing; these effects were later attenuated by yohimbine (5 nmol) pretreatment. Prazosin (10 nmol) also decreased clonidine-induced suppression of lever pressing, whereas neither prazosin (10 nmol) nor naloxone (10 nmol) caused any alteration in the suppression effects of clonidine on drinking and licking. None of these antagonists alone changed an individual rat's preestablished behavioral baselines. In experiment 2, the endogenous catecholamine levels, were determined in frontal cortex, hypothalamus, brainstem, dorsal obex area and adrenal glands. During the SIP situation, both the epinephrine level in adrenal glands and the norepinephrine level in hypothalamus were elevated.     

Absence of post-fast food compensation in the golden hamster (Mesocricetus auratus).

Ad lib food intakes and body weights were measured for hamsters fed one of 4 different diets. Animals were then placed on an intermittent starvation (IS) schedule in which food was available ad lib on alternate days only. Hamsters of both sexes showed little or no post-fast food compensation, i.e., after 24 hr of food deprivation their daily food intake was no greater than their daily intake during baseline testing. These animals lost a large percentage of their initial body weight and many of them died. Other hamsters restricted daily to half-day feeding periods that nearly coincided with the light (L) or dark (D) phases of the illumination cycle also failed to show food compensation; they generally ate no more during D- or L-periods that followed a half day of food deprivation than during D- or L-periods that succeeded a half day of ad lib feeding. These animals lost substantial portions of their initial body weight and many died. Hamsters refed after a 96-hr fast and an 18% loss in body weight also did not increase their food intake substantially above baseline values. In each of these experiments substantial portions of the body weight lost during starvation were not regained during extended ad lib refeeding regimens. These findings contrast strikingly with the behavior of rats tested concurrently; rats showed a dramatic post-fast hyperphagia, rapid recovery of body weight lost during starvation, and a reversal of the normal nocturnal feeding pattern when refeeding began during L-periods. Hamsters' nocturnal rhythms of eating and drinking were remarkably stable in the face of all the experimental manipulations. However, hamsters, as well as rats, were quite effective in compensating for changes in diet density; a 1:1 dilution of a liquid diet produced a prompt doubling in the volume of diet ingested. Impressive but less complete compensation was recorded when solid diets were diluted with inert substances (kaolin, cellulose). Hoarding and perhaps hibernation rather than compensation may have evolved as adaptations to periods of food scarcity. Noncompensation may be related to hamsters' nonresponsiveness to some signal of energy depletion. The possibility of lipogenesis being a rate-limiting step is considered. The desirability of adequate field data as a prerequisite to laboratory analysis of feeding behavior is emphasized.     

Effects of food restriction and adrenalectomy in rats with VMH or PVH lesions

The effects of adrenalectomy in rats with ventromedial or paraventricular hypothalamic lesions have been studied in two experiments. Rats with ventromedial hypothalamic lesions or lesions in the paraventricular nucleus were allowed to gain weight for fourteen days at which time they were adrenalectomized. Before adrenalectomy, animals with VMH lesions ate more, gained significantly more weight than animals with lesions in the paraventricular nucleus, and both were significantly heavier and consumed more food than sham-operated controls. Following adrenalectomy, food intake decreased and both groups of lesioned animals lost weight. The animals with VMH lesions stabilized at weights above the control animals. Implantation of corticosterone enhanced weight gain and food intake in animals with lesions in either the paraventricular nucleus or the ventromedial hypothalamus. In the second experiment, one subgroup of rats with VMH lesions was adrenalectomized, and allowed to eat ad lib. Two other groups of sham-operated rats with VMH lesions served as controls. One group ate ad lib and one group was pair fed to the food intake of the adrenalectomized VMH-lesioned rats. Weight gain in the adrenalectomized VMH-lesioned rats and the pair-fed VMH-lesioned controls was similar and less than the VMH-lesioned rats eating ad lib. GDP binding to interscapular brown adipose tissue was related to the degree of weight gain, not to the presence of the VMH lesion. These data show that corticosterone is essential for the expression of obesity in both PVH- and VMH-lesioned rats. They also argue that the reduction in the activity of the sympathetic nervous system of VMH-lesioned rats as estimated by the GDP binding to mitochondria from brown adipose tissue is associated with hyperphagia.     

Overcompensation of food intake following brief periods of food restriction

Four adult female Sprague-Dawley rats, maintained on an ad lib feeding schedule were deprived for either 0, 0.5, 1, 2, 4, 6, or 8 hours during the dark phase of the day-night cycle. It was found that the latency to initiate the first meal following the deprivation was independent of the previous deprivation interval. The animals were found to overcompensate for the periods without food by eating a large initial meal that increased proportionately in size with the duration of food restriction. Furthermore, the animals continued to overeat throughout the day. This deprivation-induced overeating by the animals resulted in an overcompensation in total food consumption that was 21–56% greater than on control days. The role of food intake as a regulator of body weight is discussed.     

Schedule-induced polydipsia in the mouse

Four mice were given a food pellet every 150 sec for 3 hr. All animals developed polydipsia. When the scheduled feeding was discontinued, water intake decreased. Polydipsia redeveloped following the reintroduction of the schedule immediately or after nine days of ad lib feeding. High negative correlations existed between water intake and body weight in all animals.     

Step-like DRL schedule change effects on blood chemistry, leukocytes and tissue in rats

Male albino rats maintained at 80% free-feed body weight were trained daily for two weeks on DRL 6-sec schedules and either suddenly shifted to DRL 12-sec schedules or maintained on DRL 6-sec. Within 30 min, 1 day, 3 days or 7 days after the step-like schedule change, the rats were killed along with ad lib food controls. Wet tissue weights for adrenals, spleens, testicles and pituitaries were taken and 20 different blood serum constitutents were measured automatically on a SMAC unit. Although the rats that had been shifted from the DRL 6-sec to DRL 12-sec condition demonstrated the usual marked elevations in response/reinforcement ratios, only alkaline phosphatase, SGOT and relative blood lymphocyte numbers differed significantly from the DRL 6-sec controls; tissue weight differences were not apparent. Highly significant differences existed between the 80% body weight, DRL tested rats and the non-tested, ad lib controls for: glucose, blood urea nitrogen, chloride, carbon dioxide, calcium, alkaline phosphatase, SGPT, triglycerides, relative testicle weights, absolute spleen weights, and body weight.     

Defense of a lowered weight maintenance level by lateral hypothamically lesioned rats: Evidence from a restriction-refeeding regimen

Male rats maintained their body weight at approximately 85% that of sham-lesioned controls following lesions of the lateral hypothalamus (LH). One month following surgery, the food intake of half the LH-lesioned animals was restricted until their body weight had declined to 80% that of nonrestricted LH animals. Half the sham-lesioned animals were similarly restricted until their body weight fell to 80% that of nonrestricted control animals. When returned to an ad lib feeding schedule, both restricted groups were initially hyperphagic and quickly restored their body weights to the level of the nonrestricted group from which they were originally selected. In doing so, the LH animals increased their food intake by the same amount and took the same number of days to restore their weight to control levels as the sham-lesioned animals. These observations provide further evidence of the vigor and effectiveness with which LH animals defend their reduced level of maintained body weight.     

Refeeding after differential severity of deprivation

Forty-eight female rats were randomly assigned in equal numbers to an eight-day 0, 20, 23, 23.5, 46-hour food deprivation schedule, or complete starvation, followed by two weeks of ad lib refeeding. Two of the completely starved subjects died. Due to decreased metabolic need of the animals after weight loss, daily food intake was considered relative to body weight. Water consumption relative to body weight increased by the end of deprivation except for animals unadapted to deprivation. The major findings during refeeding were: (a) post-starvation anorexia does not occur after any form of starvation (scheduled or complete) when body weight is considered; (b) instead of being highest on the first day of refeeding, food consumption slowly increases to a maximum and then returns to ad lib control level; (c) the more severe the deprivation, the longer time for food consumption to reach its maximum and return to control levels; (d) the more severe the deprivation, the greater the maximal food consumption.     

Effects of forced exercise on the food intake of rats maintained on a 23-hr deprivation schedule

Adult male rats of the Sprague-Dawley strain were given daily forced exercise of progressively higher levels on motor-driven treadmills while maintained on a 23-hr food deprivation schedule. Food intake measures were taken for 68 days, spanning a range of 2–8 hr exercise-sessions per day (1–4 hr actual running time) at 1.46 km/hr. The food intake of both exercising and sedentary food-restricted animals was lower as compared to that of ad lib feeding animals. Exercise did not further suppress food intake. Shifts to higher exercise levels did not result in any transitory or permanent depression in food intake. It is concluded that high levels of exercise in trained male rats maintained on a 1-hr/day feeding schedule has no suppressive effects on food intake.     

The effect of increased adiposity on food intake of juvenile rats

The regulation of feeding by body adiposity, as proposed by the lipostatic theory, has been well demonstrated in adult animals. However, mechanisms controlling long-term feeding in juvenile animals have not been well defined. In this study, increased adiposity was induced in young rats through oral gavage. Four-week-old rats were divided into three groups; ad lib feeding (100%-AL), tubefed 100% (100%-TF) or 150% (150%-TF) of ad lib intake. Animals were tube-fed these levels for one week. At the end of this period, one third of each group were killed and all remaining animals were returned to ad lib feeding for either 4 or 29 days later. During this recovery period, the 150%-TF group had significantly depressed food intakes for the first 4 days in comparison to the 100%-TF group. Afterwards, there were no significant differences between these two groups for the remainder of study. Overfeeding induced significant increases in total body fat in the 150%-TF group (24.8 grams) in comparison to the 100%-AL group (11.0 grams) and the 100%-TF group (14.0 grams). By day five of recovery, only the 150% group exhibited a significant loss of body fat. Total carcass protein and ash were not different between groups at any period. At day 29 of recovery, there were no treatment differences in carcass weight or fat content. Loss of body fat from the 150%-TF rats was associated with the decline in caloric intake. It appears that food intake is affected by relative adiposity during the dynamic phase of growth.     

Effect of a high-fat diet on firing rate of sympathetic nerves innervating brown adipose tissue in anesthetized rats

Three experiments have examined the effects of ad lib and forced intake of a high-fat diet on sympathetic firing rate to brown adipose tissue. Seven days after beginning of ad lib intake of either a low-fat or high-fat diet, sympathetic activity was not significantly different in either group nor was it significantly different from the values obtained in animals measured at the switch from the chow to a semisynthetic high- or low-fat diet. After 22 days on the semisynthetic diet, however, the sympathetic firing rate of animals eating the high-fat diet had decreased nearly 25% and was significantly lower than the animals maintained on the semisynthetic low-fat diet or animals studied at the transition from the chow to the low-fat diet. In a second experiment animals were tube-fed for 3, 6 or 9 weeks on a high- or low-fat diet. Sympathetic firing rate of the rats eating the low-fat diet was higher at all three times, but the difference decreased with longer feeding. To eliminate differences in food intake, animals were tube-fed a moderate- or high-fat liquid diet three times a day for six days. The 80 kcal/day intake produced a steady weight gain in both groups. Liver weight, retroperitoneal white adipose tissue weight, and interscapular brown adipose tissue weight were all significantly greater in the animals fed the high-fat diet. Sympathetic firing rate, however, was significantly lower in the animals fed the high-fat semisynthetic diet as compared to animals fed the moderate-fat diet. These data show the high-fat diets are associated with a reduction in sympathetic activity to brown adipose tissue.