Recovery of anticipatory activity to restricted feeding in rats with ventromedial hypothalamic lesions

Entrainment of circadian activity rhythms to a fixed daily mealtime was measured in intact and ventromedial hypothalamic (VMH) lesioned rats housed in tilt-cages. Intact rats showed a clear increase in activity for 2–3 hr prior to the 2 hr daytime feeding period. Anticipatory activity in lesioned rats was attenuated or absent during restricted feeding 5–9 weeks after surgery, but was evident in all rats, even those bearing apparently total VMH damage, during a second restricted feeding schedule 14–21 weeks after surgery. These results show recovery of function and argue against a necessary role for the VMH in food entrained rhythms.     

Disruption of diurnal feeding and weight gain cycles in weanling rats by ventromedial and dorsomedial hypothalamic lesions

At the age of 28 days, male Sprague-Dawley rats received bilateral electrolytic lesions in the ventromedial (VMN) and dorsomedial (DMN) hypothalamic nuclei, repectively. Sham-operated rats served as controls. Food intake and body weight gains were measured for 13 days at the beginning of the light period (0800–2000 hr) and prior to the start of the dark period (2000-0800 hr). Both types of hypothalamic lesions caused a disruption of the naturally occurring diurnal feeding and weight gaining cycles. In accordance with previous data, the VMN rats remained normophagic and made normal weight gains while DMN animals were hypophagic and gained weight subnormally; linear growth was reduced in both types of lesioned animals, but only the VMN rats became obese. The data suggest the existence in the medial hypothalamus of an area that is involved in feeding and weight gaining cycles. From the standpoint of overall-caloric intake, this area consists of two types of neuronal assemblies that differ fuctionally as profoundly as they are anatomically separate.     

Reduced salivation in rats following ventromedial hypothalamic lesions

Salivation was assessed in normal rats and rats with bilateral lesions of the ventromedial hypothalamus (VMH). VMH lesioned rats demonstrated a reliable reduction of salivation. This hyposalivation occurred during a one month period that animals were maintained on dry rat chow and for a 16 day period that animals were maintained on a palatable liquid diet. VMH rats did not differ from control rats in the amount of saliva secreted in response to Prostigmin or wintergreen solution. Thus, while the VMH rat shows a reduced basal salivation level, such animals salivate normally in response to a strong taste substance.     

Deficits in glucose appetite and satiety produced by ventromedial hypothalamic lesions in the rat

Rats with ventromedial hypothalamic lesions displayed a reduced sensitivity to dilute (5 or 7%) glucose solutions. The lesioned animals were less responsive to the food suppressive effects of glucose ingestion, and they drank less dilute glucose when food deprived compared to controls. The VMH lesioned rats, on the other hand, appeared normally sensitive to concentrated (20 or 33%) glucose solutions. They suppressed their feeding in response to glucose intubation, and they consumed more concentrated glucose solution than did controls, which is consistent with the hyperphagia effects of the lesions. The nature of the neural impairment responsible for these lesion effects is discussed.     

2-deoxy-D-glucose inhibits food intake in rats after ventromedial hypothalamic lesions

Changes in food induced by 2 deoxy-D-glucose (2 DG) have been investigated in newly lesioned rats during the two parts of the diurnal cycle. In a first experiment rats were injected with saline or 2 DG (250, 500, 750 mg/kg) at the beginning of the light or the dark period. In a second experiment rats were injected with saline or 2 DG (250 mg/kg) in the middle of the two periods after 0, 2, 4 or 6 hr of fasting. Results show that 2 DG exerts an inhibitory effect on food intake at night, as it does in intact rats, under ad lib conditions or after a short deprivation time. The stimulating effects of 2 DG on diurnal food intake observed in intact rats is not replicated in VMH rats. On the contrary an inhibition of intake follows a short food deprivation. The data suggest that 2 DG stimulates food intake only under metabolic and feeding conditions characteristic of the diurnal phase in intact rats. Since lipogenesis and hyperphagia are observed 24 hr a day in VMH animals, only inhibition could follow 2 DG.     

Effects of restricted daily feeding on freerunning circadian rhythms in rats

Male rats were kept in conditions of constant dim illumination and alternately fed ad lib or for 2 or 4 hr per day only. Locomotor activity was recorded as wheel running and as activity in the cage by a microphone system. At selected days before, during and after restricted feeding (RF) blood samples were taken from the tail in 4-hr intervals for the determination of plasma corticosterone. Under both schedules of RF, the circadian rhythms of activity and of plasma corticosterone continued to freerun without significant changes in period or phase while the feeding times were anticipated by increases in activity and in plasma corticosterone. After the termination of RF, the anticipatory components persisted for several days and merged into the freerunning rhythms through transients. The results support the concept of two systems with oscillatory capacities: the freerunning system which is driven by a pacemaker and not affected by RF, and the anticipatory system which can be uncoupled from the freerunning system by an entraining feeding cycle.     

Effects of ventromedial hypothalamic lesions on rat ethanol intake

The consumption of food, water and ethanol solutions, in free choice condition, was studied in 9 rats with electrolitic lesion of ventromedial hypothalamus, before and after the operation and compared with 2 controls submitted to sham operation. Changes in body weight were studied between 20 and 30 days after the operation. In all the experimental rats there was an increase in food, water consumption and body weight while ethanol intake decreased significantly.     

Preoperative experience with insulin enhances glucoprivic feeding in rats with lateral hypothalamic lesions

Adult male Sprague-Dawley rats received either one injection per week of regular insulin (IP, 5 Units) or saline for 4 weeks prior to destruction of the LH or sham-operations. During this preoperative period, animals given insulin consumed significantly more food in a 6-hr test period than animals given saline. Following surgery, animals were given 3 weeks to recover from the acute effects of LH lesions and then tested for responsiveness to glucoprivic challenges. Sham-operated animals from both pre-operative injection groups consumed significantly more food during a 6-hour period when injected with either insulin (5 and 7.5 Units) or 2-DG (400 mg/kg) than when given saline injections. Similarly, LH-lesioned rats with preoperative experience with insulin significantly increased food intake when given insulin or 2-DG. In contrast, LH-lesioned rats without preoperative experience with insulin failed to increase feeding in response to the administration of either insulin or 2-DG. Differences in feeding responses following glucoprivation between LH-lesioned rats with and without preoperative exposure to insulin were not a function of differences in the extent of central nervous system damage. The present data indicate that experimental conditions play an important role in determining the presence or absence of regulatory deficits following brain damage.     

Effects of restricted feeding on single neuron activity of suprachiasmatic neurons in rat hypothalamic slice preparation

Influence of restricted feeding on single neuron activity in the rat suprachiasmatic nucleus (SCN) was examined using hypothalamic slice preparations. Feeding restriction for one month did not change SCN neuron activity in either normal light-dark schedule (LD) or constant light schedule (LL). Locomotor activity in vivo was increased for a few hours before and during feeding time by food restriction of both LD and LL rats. The present experiment suggested that the memory of feeding time produced by food restriction is independent of SCN neuron activity.     

Sham feeding in rats after ventromedial hypothalamic lesions and vagotomy

Sham feeding was examined in female rats with ventromedial hypothalamic (VMH) lesions with or without abdominal vagotomy. In Experiment 1, intact rats consumed more than twice as much sweet milk during 1-hr tests of sham feeding (M = 13.0 ml) as they did when feeding normally (M = 5.5 ml). Rats with VMH lesions showed exaggerated sham feeding, which was elevated almost fourfold (M = 56.6 ml) over their already high normal feeding baseline (M = 15.1 ml). In Experiment 2, vagotomy substantially reduced sham feeding in rats with VMH lesions. After vagotomy, VMH rats sham fed half as much (M = 23.7 ml) as nonvagotomized VMH rats did (M = 46.8 ml). Vagotomy did not, however, reduce sham feeding to control levels (M = 13.1 ml). These results are consistent with the hypothesis that VMH hyperphagia arises from exaggeration of orosensory responsiveness, which is, in part, a consequence of perturbed vagal function.     

Effects of lateral hypothalamic lesions on consummatory behavior in developing rats.

Bilateral lesions aimed at the lateral hypothalami of preweanling rats result in decreased weight gain and eventual death within 5 days after the operation. Ten-day-old rats with unilateral damage to the lateral hypothalamus show retarded growth, food and water intake regulatory deficits, and altered sensitivity to quinine adulteration of the water for up to 60 days of age. These results suggest that at least one neural mechanism that regulates food and water intake matures early in the postnatal life of the rat.     

Impaired free-operant avoidance behavior following ventromedial hypothalamic lesions in rats

Under each of 3 shock intensities, ventromedial hypothalamic lesioned rats emitted fewer responses and received more shocks than control animals in a lever-pressing free-operant avoidance paradigm. While the performance of the control animals improved across 10 days of testing and within each session, the between- and within-session performance of the lesioned rats, after improving moderately during the first few days of testing, deteriorated as training progressed. Although the response rates of the lesioned animals were relatively unrelated to the different current levels, their shock rates varied inversely with intensity. This resulted from an increase in the frequency of long interresponse times and a reduction in the number of consecutive shocks. Preoperative training substantially improved the avoidance behavior of lesioned animals, but their postoperative performance was nevertheless inferior to their preoperative levels.     

Effects of amphetamine and phenylpropanolamine on food intake in rats with ventromedial hypothalamic or dorsolateral tegmental damage

Female rats with sham lesions or lesions of the ventromedial hypothalamus (VMH) or the dorsolateral tegmentum (DLT) were maintained at 80% normal body weight to minimize possible group differences in hunger motivation. VMH rats displayed attenuated amphetamine (0.5, 1.0, and 2.0 mg/kg) anorexia when fed a high-fat test diet but normal anorexia when fed a pellet test diet whereas DLT rats displayed attenuated amphetamine anorexia when fed either test diet. Neither VMH nor DLT rats displayed attenuated anorexia to phenylpropanolamine (5.0, 10.0, and 20.0 mg/kg), an analogue of amphetamine. These results are discussed in terms of an amphetamine-activated arousal mechanism within the DLT.     

The effects of restricted food access upon locomotor activity in rats with suprachiasmatic nucleus lesions

The purpose of the study was to investigate the ability of rats with suprachiasmatic nucleus (SCN) lesions to anticipate restricted food access (RFA). The sham operated controls demonstrated entrainment of locomotor activity to a LD 12:12 cycle with ad libitum food and water, while the lesioned animals were arrhythmic in their running behavior. When exposed to constant light (LL) and presentation of food once every 24 hours, anticipatory wheel running was observed in both groups. A return to ad lib food and the previous LD 12:12 schedule produced a slow re-entrainment of running in the controls and arrhythmic activity in the SCN animals. The results suggest that the SCN is not necessary for the appearance of locomotor rhythms in the rat.     

Effects of anterior hypothalamic lesions on the sexual behavior of prenatally-stressed male rats

Sprague-Dawley females were exposed to the stress of heat, restraint and bright lights during the third trimester of gestation. Virtually all male offspring tested for masculine sexual behavior as adults ejaculated and copulated with lure females. Also prenatally-stressed males exhibited two to three times as many lordotic responses as did males from nonstressed mothers. Because animals were crossfostered, an in utero action of prenatal stress is supported. Anterior hypothalamic (AHA) lesions significantly reduced the number of lordotic responses observed in prenatally-stressed male rats compared to those observed in prenatally-stressed males bearing sham lesions of the AHA. The possibility is presented that prenatal stress may influence the developing male brain.     

Factors influencing active avoidance behavior in rats with ventromedial hypothalamic lesions

Ventromedial hypothalamic lesioned rats maintained at preoperative body weight received an equal number of shocks while emitting significantly fewer responses than controls in a lever-pressing free-operant avoidance paradigm, and performed as well as unoperated animals in lever-pressing and shuttle box (both 1- and 2-way) discriminated avoidance tasks. The failure of VMH lesions to facilitate performance in the 2-way avoidance paradigm was probably the result of a ceiling effect. With the exception of the simple one-way avoidance task, obese lesioned rats were markedly impaired in the acquisition of all active avoidance behavior, but escape behavior was not affected. When tested in a free-operant paradigm, the avoidance performance of well trained lesioned animals varied inversely with body weight. As obese rats displayed lower flinch thresholds to shock than controls and similar levels of activity and responding as lean lesioned animals, it was concluded that their impaired avoidance behavior was not due to changes in sensitivity or mobility. The possible relation to other VMH lesion- and/or obesity-induced deficits is discussed.     

Ingestive behavior in adult rats with dorsomedial hypothalamic lesions

Large lesions in the dorsomedial hypothalamus (DMH) resulted in transient hypophagia that produced a significant weight loss. Energy intake per g of body weight returned to normal levels within 2 weeks after surgery but the body weight loss incurred during the immediate postoperative period was not compensated in 3 months of observation. The experimental animals responded poorly, if at all, to 2-deoxy-D-glucose induced cellular glucoprivation but ate normally after 2 doses of insulin and compensated appropriately for 24 hours of food deprivation. Rats with DMH lesions also displayed persisting hypodipsia (even when the animals' reduced body weights were taken into account) but responded normally, or nearly so, to water deprivation (with and without food), cellular dehydration, or extracellular hypovolemia. (Rats with DMH lesions drank slightly less than controls on most of these tests even when their chronically lowered body weights were taken into account but the impairment was small and, in most instances, not statistically reliable.)     

Persistent depression of wood-gnawing following ventromedial hypothalamic lesions in the rat

Female rats with ventromedial hypothalamic lesions that resulted in hyperphagia and obesity displayed chronically reduced levels of wood gnawing that persisted for more than 200 days post-operatively. Reduced wood gnawing was apparent even when the animals were totally deprived of food, thus ruling out the possibility that the effect was secondary to hyperphagia.     

Feed efficiency in growth-retarded rats with ventromedial and dorsomedial hypothalamic lesions produced shortly after weaning

Weanling male rats received electrolytic lesions (L) in the ventromedial (VMN) and dorsomedial (DMN) hypothalamic nuclei; sham-operated rats served as controls. The animals were maintained for various periods up to 50 postoperative days on lab chow under standard conditions. In a short-term study, food intake and body weights were measured daily and body weight gain was divided by the food eaten to obtain the efficiency of food utilization. Also, gains in metabolic size ($\text{kg}\text{3}\text{4}$) were divided by food eaten. Both manipulations showed that DMNL rats, except for the first two postoperative days, utilized food normally. The same changes were obtained for weanling VMNL rats, except that they did not show a decline in utilization during the first two postoperative days. Computation of efficiency of food utilization for both VMNL and DMNL rats over postoperative durations ranging from 7 to 50 days showed that among 12 out of 14 experiments DMNL rats utilized food as well as controls. Out of 8 experiments, rats with VMNL utilized food better for weight gained than controls in one and poorer than controls also in one experiment; in reference to metabolic size they utilized food normally. The foregoing data, gathered from 225 DMNL, 64 VMNL and 181 control rats show quite convincingly that food utilization in both types of experimental animals is unimpaired despite profound reductions in ponderal and linear growth and food intake in the DMNL rat and reduced circulating growth hormone levels in the VMNL rat.     

Passive avoidance behavior in lean and obese rats with ventromedial hypothalamic lesions

Lean and obese rats with ventromedial hypothalamic lesions performed reliably worse than control animals in the acquisition of a step-down passive avoidance task. However, obese rats performed significantly better than lean VMH animals, which consistently leaped off the platform on the second and succeeding trials. While there were no significant differences between groups in the acquisition of a step-through passive avoidance task, lean and obese rats with VMH lesions took reliably longer than control animals to reach criterion when an identical step-through response had previously been reinforced (punishment-extinction of a one-way conditioned avoidance response). Both lean and obese VMH-damaged rats made more punished approach responses to water than control animals following water-deprivation to 88% of body weight, but only lean VMH rats made a significantly greater number of punished approach responses to liquid food than unoperated animals following food-deprivation to 88% of body weight. The number of punished consummatory responses appeared to be influenced by baseline intake. Among the animals tested in more than one paradigm, there was a significant positive correlation between the number of punished consummatory responses and the number of shocks received during punishment-extinction of the one-way CAR, but no relationship was observed between the performances in either of these and the step-down avoidance paradigm. The impaired passive avoidance behavior by rats with VMH lesions is attributed to both an inability to inhibit a previously reinforced response and a change in response tendencies to aversive stimuli.