Lesions in the amygdala and the frustration effect

Responding in a double runway following the omission of reinforcement in the first goal box was investigated in rats with lesions in the amygdala. Analysis of runway speeds indicated that bilateral lesions in the amygdala prevented the occurrence of the frustration effect in the second alley and produced decreased vigor of performance in the first alley. Results were discussed in terms of frustration and changes in motivation.     

Aftereffects of rewarding lateral hypothalamic brain stimulation and feeding behavior.

The aftereffects of rewarding lateral hypothalamic brain stimulation are shown to depress the speed with which rats will initiate consumption of various foods. The strength of this depression was positively correlated (r_xy = 0.60) with the rate of self-stimulation on that electrode. Seemingly paradoxical relations between this finding and other known characteristics of lateral hypothalamic stimulation are discussed.     

Alterations in ingestive behaviors after bilateral lesions of the amygdala in the rat

Bilateral electrolytic lesions in the dorsal aspect of the central amygdaloid nucleus of the rat produced aphagia and adipsia which was similar to but not as severe as or identical to that observed with lesions of the lateral hypothalamus. After tube-feeding to recovery these animals showed permanent deficits in motor coordination as well as in their ability to respond normally to external stimuli. Lesions in the same lateral plane but more ventral or posterior produced none of these changes. An immediate mild, transient hyperphagia was produced by lesioning the ventral posterior aspect of the lateral amygdala, and an impaired neophobic response was observed by lesioning the dorsal aspect of the lateral amgdala. These studies show that it is possible to localize discrete areas in the amygdala which have specific effects on ingestive behaviors. It is suggested that the amygdala modulates on-going hypothalamic activity via the stria terminalis from the dorsomedial area and the ventral amygdalofugal pathway from the ventral and lateral amygdala.     

Modulation of hypothalamic ICSS by concurrent limbic stimulation

Four rhesus monkeys were surgically implanted with arrays of subcortical electrodes and trained to self-administer rewarding electrical stimulation (ICSS) to the hypothalamus. In all four animals, concurrent electrical stimulation of the CA3 region of uncal anterior hippocampus or of the cortico-medial region of amygdala inhibited hypothalamic ICSS. In two of the four animals, concurrent stimulation of the more posterior hippocampus (CA3) facilitated ICSS. Concurrent stimulation of other areas (including basolateral amygdala, hippocampal CA4 region, internal capsule, optic tract, thalamus, and caudate nucleus) had no effect on hypothalamic ICSS. It is suggested that hypothalamic reinforcement processes may vary according to the parameters of limbic involvement.     

Self-stimulation of a hypothalamic site in response to tension or fear.

Rats depleted of sodium by the IP injection of 10% b.w. of isotonic glucose for 30 min, developed a specific sodium appetite. The blood volume decreased 16% of the control value immediately after the treatment, returning to normal levels 2 to 4 hr later. The plasma sodium concentration showed a sudden and significant decrease, returning to control value 10-12 hr after the dialysis. In contrast, the sodium appetite became evident 10-12 hr after dialysis and reached the highest volume of ingestion at the sixteenth hr when both volemia and natremia had returned to normal. Since the appearance of the sodium appetite was not initiated during the state of hypovolemia and hyponatremia, the results show that the decrease in plasma volume and sodium concentration of the intravascular fluid that occurs after acute sodium depletion by IPD does not initiate an immediate onset of the sodium appetite.     

Effect of lesions in the amygdala on behavioral contrast

Amygdalectomy in rats prevented the occurrence of behavioral contrast. After the animals were trained to lever press on a multiple schedule where responses were reinforced on the average of once per min in two alternating components, one component of the multiple schedule was switched to extinction while reinforcement in the other component remained unaltered. Response rates during the unaltered component increased significantly over pre-change rates in that component (i.e., behavioral contrast) for the controls, but remained substantially unchanged for animals with amygdala lesions. Response rates were clearly differentiated in the reinforced and nonreinforced components for both groups, signifying that discrimination between the two reinforcement contingencies was not impaired in the amygdala group. The lack of contrast in the latter group was attributed to a reduction in extinction-induced emotionality resulting from the lesion.     

Self-stimulation of the lateral hypothalamus and ventrolateral tegmentum: excitability characteristics of the directly stimulated substrates

Recovery from refractoriness in the neural substrate for self-stimulation of the ventrolateral tegmentum (VLT) was estimated using psychophysical techniques, and compared to recovery in the substrate for self-stimulation of the lateral hypothalamus (LH). A computer-controlled testing setup was developed to minimize experimenter error and testing time. In order to assess the performance of this setup, refractory period estimates obtained in the newly designed, computer-controlled equipment were compared to those obtained in the hand-operated equipment used in previous experiments of this type. No meaningful differences were found. Thus, the more convenient computer-controlled setup was used to collect refractory period estimates from the VLT and LH. A comparison of these values revealed differences in the slopes of the recovery curves, and in the C-T intervals bracketing their rising portions. The VLT curves rose more gradually, and both began to rise and levelled off at longer C-T intervals than the LH curves. One explanation of these results is that the distribution of excitability in the LH substrate is shifted towards higher values than the VLT distribution. The overlapping portions of the recovery curves could reflect the contribution of a common bundle of reward-related fibers.     

Self-stimulation in the sheep: Interactions with ingestive behaviour and light cycle

Self-stimulation was obtained in 5 adult male sheep using a movable electrode system. The effects on response rate of increases in current, food deprivation and satiation were determined. Interactions between feeding, drinking and self-stimulation over longer periods (5 days) were studied in experiments in which individual sheep lived in an isolated continuously illuminated pen. Experimental conditions were as follows:—(1) Food + water available on operant (FR 30); (2) Operant food and water + self-stimulation; (3) Bowl feeding, ad lib water + self-stimulation; (4) As for condition‘3’ but with 12:12 light/dark cycle. Finally, sheep were tested for stimulation-bound feeding and drinking. The results obtained in these experiments with the sheep, a ruminant, are compared with those previously found for the pig.     

Sleep-related neurons in the central nucleus of the amygdala of rats and their modulation by the dorsal raphe nucleus

The amygdala (AMY) plays an important role in initiating appropriate neurobehavioral responses to emotionally arousing events. Its major efferents from the central nucleus (Ace) to the basal forebrain, hypothalamus and brainstem permit it to influence sleep mechanisms. To characterize further the neuronal activity of AMY during sleep and wakefulness, we recorded single neuronal activity in Ace across behavioral states in freely moving, normally behaving rats. Of the 49 neurons recorded from Ace, 24 neurons had firing patterns related to sleep-wakefulness (S-W). Of these, 50% (n = 12) had a high firing frequency during wakefulness (W) or both W and REM sleep (REM), 12% (n = 3) were non-REM (NREM)-related, 17% (n = 4) had a high firing rate in REM (REM-ON), and 20% (n = 5) fired at a low rate during REM. Because serotonin introduced into AMY during REM induces short-latency changes of state, we also studied the effects of low frequency (1 Hz) electrical stimulation of the dorsal raphe nucleus (DRN) on Ace neurons. All REM-ON neurons recorded from Ace were inhibited by DRN stimulation, and other cell types were unaffected. Thus, we found that the majority of cells in Ace related to S-W fired slowly during NREM and increased their discharge during W and/or REM, and that the DRN has the potential for modulating the spontaneous activity of REM-ON cells in rats.     

Perifornical fiber system mediates VMH electrically-induced suppression of feeding

Fiber pathways mediating the cessation of food ingestion during continuous low-level electrical stimulation of the ventromedial region of the hypothalamus (VMH) were appraised in food-deprived male rats using knife cuts. Parasagittal knife cuts in the medial perifornical area of the hypothalamus produced much larger increases in threshold current intensities for the inhibition of feeding than did cuts in the lateral perifornical hypothalamus. These findings indicate that fiber pathways critical to the inhibitory feeding effect of continuous VMH electrical stimulation traverse the perifornical hypothalamus but not the lateral hypothalamus. A comparison of these and other results demonstrates an anatomical similarity between the fiber pathways mediating VMH electrically-induced inhibition of feeding and hypothalamic hyperphagia following lesions or knife cuts. The nature of the inhibitory feeding effect of VMH electrical stimulation is also addressed and behavioral observations strongly supportive of a specific anorectic effect produced by the stimulation are reported.     

Attenuation of a convulsive syndrome in the rat by lateral hypothalamic stimulation.

Modification of a behaviorally suppressive syndrome produced by cholinergic activation of the amygdala was compared under automatically delivered electrical stimulation in rats which had previously been implanted with a bipolar electrode in the medial forebrain bundle (MFB) and preselected for high or low self-stimulation rates. Carbachol was applied bilaterally to the amygdaloid complex to precipitate a convulsive syndrome. Concurrently, brain stimulation pulses were applied unilaterally to the medial forebrain bundle at the lateral hypothalamic level at predetermined current intensities and frequency in two program combinations: ON-OFF-ON and OFF-ON-OFF. The rats were assigned scores on 5 measures of the carbachol-induced syndrome, as well as on a locomotion measure. An irritability test was also administered 6 times during the test hour. The frequency of clonic seizures was found to be significantly lower for all self-stimulators, especially those in the ON-OFF-ON order of ICS. Greater locomotor activity was found for experimental self-stimulators. Non-self-stimulators were most characterized by muscular hypertonus and seizure activity, and were indistinguishable from the carbachol-only controls on the locomotion measure. Other aspects of the syndrome appeared to be unaffected. The results are discussed in relation to the concept of a behavioral facilitative-suppressive model, and a possible neuroanatomical substrate consisting of mutually-antagonistic noradrenergic and cholinergic systems.     

Bilateral kindled amygdala foci and inhibitory avoidance behavior in rats: A functional lesion effect

The repeated administration of brief low level electrical stimulation can be used to produce latent kindled epileptic foci in discrete regions of brain. Three groups of rats with kindled amygdala foci were trained and tested on a one-trial inhibitory avoidance task. The training-retention test interval was 24 hr. Animals with bilateral foci were impaired on this task. Animals experiencing either 6 convulsions or 12 convulsions from a unilateral focus were not impaired. This result is interpreted as support for the hypothesis that a kindled focus can act as a functional lesion.     

Estradiol induced suppression of feeding in the female rat: dependence on body weight

Ovariectomy in the adult female rat leads to a transient increase in food intake and an elevated level of body weight. Estrogen treatment blocks or reverses these changes. Currently, estrogen is seen to suppress feeding directly, but earlier findings suggest that estrogen's effect is dependent upon an elevated level of body weight. We demonstrate that 1 μg estradiol, which has suppressant effects on food intake and body weight in ovariectomized (OVX) rats, has no such effects in ovariectomized-adrenalectomized (OVX-ADX) rats, which do not gain excess weight spontaneously. However, estradiol does have a suppressant effect on these measures in OVX-ADX rats, if they are made mildly obese by dietary means. Therefore, estradiol suppresses feeding only in the face of actual or impending obesity. It probably affects the system(s) concerned with the long-term regulation of body weight; but it does not act directly on the mechanisms which mobilize or inhibit feeding.     

Role of noradrenaline and serotonin in the basolateral region of the amygdala in food preferences and learned taste aversions in the rat

First, it was confirmed that bilateral lesions in the basolateral region of the amygdala (ABL) of the rat increased the time spent eating novel as compared to familiar food in a food preference test, and that the lesions impaired learned taste aversion to a sucrose solution which had been paired with lithium chloride. Then the roles of noradrenaline and serotonin in the amygdala in these aspects of food intake were investigated. In Experiment 2, it was shown that injections of 10 and 20 nmoles of noradrenaline (NA) into the ABL increased the time spent eating familiar food in the food preference test. Higher doses of NA (50 and 100 nmoles) increased the total time spent eating without changing the preference of the rats for familiar or novel food, and produced behavioral side effects. Serotonin (5HT) injected into the ABL in doses of 10, 50 and 100 nmoles did not modify the pattern of choice of the foods. In Experiment 3, it was shown that depletion of NA in the ABL with 10 micrograms 6-hydroxydopamine did not alter the level of feeding of novel and familiar foods, but did impair taste aversion Depletion of 5HT in the ABL with 10 micrograms 5,7 dihydroxytryptamine did not alter food preferences or impair the taste aversion learning. The depletions of NA and 5HT were confirmed biochemically. These results provide further evidence for a role of the amygdala in preferences for novel as compared to familiar foods and in learning that the ingestion of a food is associated with sickness, and suggest that noradrenaline but not serotonin in the amygdala is involved in these types of control of food intake.     

Acute electrical stimulation of the subfornical organ induces feeding in satiated rats

The SFO, a circumventricular organ (CVO) that lacks the normal blood-brain barrier, is an important site in central autonomic regulation. A role for the SFO in sensing circulating satiety signals has been suggested by electrophysiological studies demonstrating that the anorexigenic satiety signals, leptin and amylin, as well as the orexigenic satiety signal, ghrelin, influence the excitability of separate populations of SFO neurons. The present study examined whether acute, short duration, electrical stimulation of the SFO influenced feeding in satiated rats. Electrical stimulation (200 µA) of satiated animals with subfornical organ (SFO) electrode placement (n = 6) elicited feeding in all animals tested with a mean latency to eat of 8.0 ± 4.0 min after termination of SFO stimulation (mean food consumption: 0.6 ± 0.12 g/100 g bw). These same rats undergoing a sham stimulation did not eat (mean food consumption: 0.0 ± 0.0 g, n = 6) nor did animals receiving stimulation with non-SFO electrode placements (mean food consumption: 0.0 ± 0.0 g, n = 6). SFO stimulation at this intensity elicited drinking in 5/6 animals with a mean latency to drink of 15.2 ± 2.6 min. Feeding effects were specific to higher stimulation intensities as lower intensity stimulation (100 µA, n = 6) elicited drinking (mean latency to drink: 6.2 ± 2.6 min) but did not cause any animal to eat.The results of the present study show that acute, short duration, SFO stimulation induces feeding in satiated rats, lending support for a role for the SFO as an integrator of circulating peptides that control feeding.     

Modulation of the pair housing induced feeding suppression

The present experiments explored how manipulating the period of individual housing, partner novelty, or short periods of conspecific interaction affected the feeding suppression evident when young adult male rats were moved from individual to pair housing. In the first experiment, after a period of pair housing, rats were individually housed for 0, 3, 10, or 14 days before being rehoused with either the same or a novel partner. There was an increase in the feeding suppression as the duration of individual housing grew, and at 3 days, the novel partner produced a stronger suppression than did the familiar partner. In the second experiment, four 15-min exposures to a conspecific in a novel place preference environment did not eliminate the feeding suppression at pair housing. The third experiment found that four 90-min exposures to a conspecific reduced the feeding suppression evident at rehousing. In Experiments 2 and 3, an environment previously paired with a conspecific did not produce a place aversion. Together, these experiments suggest that the feeding suppression evident when male rats are moved from individual to pair housing can be considered a graded effect open to modulation by a variety of behavioral manipulations.     

Perceptual cues of reinforcing brain stimulations in the postero-lateral area of the hypothalamus

In order to study the perception of intracranial reward in the rat, a rewarding hypothalamic brain stimulation served as conditioned stimulus (CS) in an avoidance paradigm. The rate of self-stimulation behavior was used to estimate the strength of intracranial reward and reinforcement. Tests of stimulus generalization were performed by modifying the electrical parameters of the CS so as to form a set of substitute stimuli (SS). Results show that the discrimination gradient depends mainly on the rewarding value of the intracranial stimulation. A Stevensian power function relates the percentage of avoidance responses to the intensity of the self-stimulation behavior, which in turn was estimated by such methods as continuous reinforcement frequency, fixed ratio schedules, weight, choice, self-regulation and cost methods. Moreover, the latency of the avoidance responses is related directly to the magnitude of the self-stimulation elicited by the same brain stimulations. On grounds of this data, we assume that the internal decisional process could discriminate well between the different brain stimuli on the basis of the rewarding value produced. Differences observed between methods evaluating the magnitude of reinforcement induced by the rewarding electrical brain stimuli are thus mainly due to differences in motor performances required by each method to obtain the electrical reward.     

Analysis of feeding patterns in normal and vagotomized rabbits.

Spontaneous meal sizes, intermeal intervals, and 24 hr feeding rhythms were monitored in normal and 60 day recovered vagotomized rabbits fed solid laboratory chow. Mean sizes of meals and intermeal intervals, and the circadian distribution of food intake did not differ between the two groups, but vagotomy was associated with increased frequencies of both smaller and larger than average meals. Positive meal to postmeal interval correlations were evident in intact but not vagotomized animals, whereas vagotomized animals displayed a meal to premeal interval correlation in the light phase that was not present in normal rabbits.     

Uremic anorexia and ghrelin expression in the amygdala

Background/aims

Ghrelin can act as a signal for mealtime hunger and meal initiation. Amygdala is indispensable in appetitive behavior motivated by learned emotions. This study was to investigate the alteration of ghrelin in the amygdala of rats with chronic renal failure (CRF) and its relation with uremic anorexia.

Methods

SD rats were randomly classified into CRF group and control group (n = 16 per group). The CRF model was constructed using 5/6 nephrectomy. When plasma creatinine (PCr) and blood urea nitrogen (BUN) in the CRF group were twice more than the normal level, food intake (g/24 h) was measured and then all rats were killed for detection of ghrelin protein expression in the amygdala using immunohistochemical analysis and mRNA expression using RT-PCT. Statistics was conducted with one-way analysis of variance, Student–Newman–Keuls-q test and correlation analysis.

Results

By the 8th week after the surgery, the BUN and PCr of CRF rats exceeded double the normal level, and their food intake was obviously decreased compared with the controls (P < 0.05). The protein and mRNA expression of ghrelin in the amygdala of CRF group were significantly reduced, and there was a positive correlation between this reduction and the decrease in food intake (P < 0.05).

Conclusion

The reduction of amygdala's ghrelin in CRF rats may be associated with uremic anorexia.     

Effect of amygdalectomy on habituation and CER in rats.

Amygdalectomized, Sham operates and unoperated rats received 20 habituation trials followed by CER training during which the habituation stimulus was made a CS for 10 CS-UCS pairings. Although no reliable differences in rate of magnitude of habituation as measured by suppression ratio magnitudes and ITI durations were apparent between any groups, these same measures indicated that substantial deficits in conditioned suppression were produced by bilateral amygdalectomy. In addition the lesion produced a reliable deficit in unconditioned suppression and a slight but reliable reduction in the number of ccs of water consumed in a 24 hour period. These results are more consistent with the hypothesis that amygdalectomy interferes with the arousal of fear than with the proposals that this lesion produces deficits in habituation or in response inhibition.