Phenylpropanolamine inhibits feeding, but not drinking, induced by hypothalamic stimulation.

In rats bearing lateral hypothalamic electrodes that elicited both feeding and drinking, intraperitoneal injection of the appetite suppressant drug phenylpropanolamine (Propadrine) inhibited only feeding. This occurred whether feeding and drinking were tested simultaneously or separately. Selective inhibition of lateral hypothalamic feeding also followed injection of this drug through lateral, but not medial, hypothalamic electrode cannulas. We conclude that hypothalamically induced feeding is under some of the same pharmacological controls as spontaneous feeding, that this control may be exerted, in part, in or near the lateral hypothalamus, and that the neural systems which induce feeding and drinking during hypothalamic stimulation can be pharmacologically separated.     

Non-interaction of ventromedial and lateral hypothalamic mechanisms in the regulation of feeding and hoarding behaviour in the rat

Lesions of the hypothalamic ventromedial nucleus (VMN) led to an immediate increase in food intake but not to any increase in hoarding activity. Later, when subjects were very obese, they failed to hoard even in response to a 16-hr. deprivation schedule, although this schedule did produce hoarding if body weights were held at, or were brought down to, preoperative levels. These results indicate that the lateral hypothalamic mechanism responsible for hoarding and feeding responds to long-term nutritional factors, and that it is not directly affected by the short-term satiety mechanisms in the VMN. These findings support the hypothesis (a) that even “non-physiological” activities (e.g. hoarding, exploration) are motivated by physiological needs, and (b) that the reason these activities do not ordinarily covary with physiological drives is that, unlike the physiological drives, they are not subject to inhibition by the hypothalamic satiety mechanisms.     

The Horsley gantt medal address October 11, 1992

The concept of systemic quantization of behavior was used to study the interaction between dominant motivation and reinforcement on brain neurons. Feeding and escape were used as experimental models. Results showed that feeding and escape motivations are based on the mechanisms of ascending activating influences of lateral or ventromedial hypothalamic centers, respectively, on cortical neurons. Feeding and escape motivations evoked by electrical stimulation of hypothalamus, or the ones occurring naturally, modify the responses of single neurons of sensorimotor and insular cortex to sensory stimuli, to microiontophoretic application of neurotransmitters and neuropeptides, and especially to reinforcement. Dominant motivations are reflected in the burst-like activity and in a specific pattern of interpulse intervals of single units in various brain structures. Reinforcement transforms this activity into a regular pattern and also changes the neuronal responses of hypothalamic feeding and escape centers, to electrical stimulation and to microiontophoretic application of oligopeptides. Specific patterns of the unit responses to conditioned stimuli in the course of consecutive reinforcement was determined. After several instances of reinforcement, especially after repetitive reinforcement, the brain neurons influenced by the dominant motivation begin to produce specific protein molecules that are important for organization of an appropriate type of behavior. This process can be blocked by protein synthesis inhibitors.     

The neural pathways mediating quiet-biting attack behavior from the hypothalamus in the cat: A functional autoradiographic study

Electrical stimulation of the region of the lateral hypothalamus produced a consistent form of quiet-biting attack behavior in cats. In one series of experiments, cats, implanted with electrodes from which attack had been elicited, were anesthetized and then were injected with a bolus of ¹⁴C-2-deoxyglucose at the same time as electrical stimulation was delivered through the attack electrodes. Brains prepared for X-ray autoradiography revealed that lateral hypothalamic stimulation activated the classical medial forebrain bundle pathway supplying the septal region, diagonal band, lateral preoptic area, and ventral tegmental region. Stimulation of quiet-attack sites in perifornical hypothalamus resulted in the activation of a much more extensive projection system which included the central and lateral tegmental fields of the midbrain and pons, and central gray region, as well as the structures described above. In a second series of experiments, ³H-leucine was placed into the region of the electrode tip from which attack was elicited in order to identify more precisely the pathways arising from that site. In general, tritiated amino acid radioautography replicated the ¹⁴C-2-deoxyglucose findings. In addition, the amino acid radioautographic data revealed the presence of extensive projections from perifornical hypothalamus to such pontine structures as the nucleus locus coeruleus, motor nucleus of NV , and the lateral pontine tegmental field. The functional connections between the lateral hypothalamic “attack region” and lateral preoptic zone were also confirmed by electrophysiological methods.     

Midbrain-hypothalamic interrelationships in the control of aggressive behavior

Previous studies have suggested an involvement of the midbrain ventral tegmental area in the biting attack upon a rat elicited by electrical stimulation of the lateral hypothalamus in cats. In order assess further the relationship between these two regions, 12 cats were implanted with attack-eliciting electrodes in both the lateral hypothalamus and the midbrain ventral tegmental area. Following a lesion of the midbrain attack site, attack previously elicited from hypothalamic electrodes ipsilateral to the lesion was eliminated or significantly reduced in frequency. The attack elicited from electrodes in the hypothalamus contralateral to the lesion was unaffected. Midbrain lesions made at sites from which attack was never elicited had no effect on hypothalamically elicited attack. The midbrain lesion in some cases eliminated only certain components of the total attack pattern; for example, the approach of a cat to the rat frequently remained present while the bite was absent. Additionally, it was found that the attack elicited from rostral hypothalamic electrodes was disrupted to a greater degree by a single midbrain lesion than the attack elicited from more caudal hypothalamic electrodes. These finding are discussed in terms of the neural system mediating this form of aggressive behavior in cats.     

Aggressive behavior induced by electrical stimulation in the midbrain central gray of male rats

Electrical stimulation via electrodes implanted in the lateral hypothalamus may induce intraspecific aggressive behavior. Small electrolytic lesions placed via these electrodes resulted in a five– to tenfold increase in the current threshold for aggression. Degenerating fibers were stained by means of the Fink-Heimer method and could be followed caudally to the dorsal midbrain central gray and to the mammillary bodies. A few axons could be traced rostrally to the medial septum. Aggression could be induced from 10 of 112 electrodes implanted in the central gray; the other electrodes elicited either locomotion, vocalization, jump, or “alarm-like reactions.” The morphology of the induced aggression was similar to the morphology of the hypothalamically induced aggression, though it was often accompanied with motor disturbances and was less intense. Hypothalamic stimulation was combined with simultaneous central gray stimulation in rats with electrodes both in the hypothalamus and in the central gray. Hypothalamic thresholds for aggression could be lowered by this stimulation of the central gray, even when no aggressive responses were observed during central gray stimulation alone. This suggests that, although aggression is not manifest, electrical stimulation may activate neural tissue involved in aggressive behavior. It is concluded that in rats central gray and hypothalamus are part of the same neural network mediating intraspecific aggression.     

Motivated behaviors elicited from hypothalamus, midbrain, and pons of the guinea pig (Cavia porcellus).

Eating, drinking, biting attack, male mating behavior, and gnawing were elicited by electrical stimulation through electrodes located predominantly in a region extending from the preoptic area through the lateral hypothalamus into the ventral midbrain. Escape and digging were elicited from a parallel but more medial region that overlapped the lateral zone only in the preoptic-anterior hypothalamic area. Several differentiable vocalizations were produced from sites distributed through most, although not all, areas explored. Sites yielding painlike responses were located principally in the vicinity of the presumed pain pathway traced after anterolateral cordotomy in other species. Reward was obtained from widespread sites that were generally congruent with catecholaminergic systems as described in the rat. Although there was considerable overlap of the effective zones for many responses, their underlying mechanisms were differentiated anatomically by localized differences in their distribution or functionally by the elicitation of pure responses from some electrodes. Response mechanisms localized in the brain stem of the guinea pig generally resembled those in the rat, although there were differences in details, especially in the posterior midbrain and pons.     

Separate neural sites for d-amphetamine suppression of mouse killing and feeding behavior in rats

The present study was conducted to investigate several possible neural sites for d-amphetamine's effect on mouse killing and feeding behaviors. d-Amphetamine (10, 20, and 30 μg) injected into each lateral ventricle, suppressed mouse kiling, food, and water intake in a dose-dependent manner. Bilateral adminstration of d-amphetamine (20 μg) into the central amygdaloid nucleus abolished mouse killing behavior but did not affect feeding and drinking. By contrast, bilateral amphetamine injections into the substantia nigra, or into the ventral region of the caudate nucleus, did not suppress mouse killing behavior, but significantly decreased food and water intake. The lateral hypothalamus was sensitive to d-amphetamine injections, which suppressed mouse killing and food intake as well as water intake. d-Amphetamine injections into the nucleus accumbens produced inconsistent effects on mouse killing and feeding. Our observations suggest a differentiation of the neural sites that mediate feeding from those underlying mouse killing behavior.     

Food hoarding behaviour in the golden hamster (Mesocricetus auratus): Effects of body weight loss and hoard-size discrimination

Two experiments investigated some of the factors that influence food hoarding behaviour in the golden hamster (Mesocricetus auratus). In Experiment 1, hamsters given limited access to food failed to increase the amount of food they consumed at each meal. Instead, they exhibited a significant increase in the amount of food taken to hoard during the limited access period, and this permitted hamsters who were allowed to retain their hoard to maintain body weight at levels comparable to free-feeding controls. Hamsters that were not allowed to retain hoarded food rapidly lost body weight. There was also an inverse correlation between body weight and amount of food taken to hoard in all hamsters given limited access to food, suggesting that body weight loss was one factor directly related to increased hoarding during periods of limited food accessibility. Experiment 2 investigated the effect of hoard-size discrimination on food hoarding in hamsters by artificially manipulating hoard size. The results suggested that hoarding behaviour could be influenced by artificially depleting and repleting the hoard, and this factor appears to influence hoarding in the absence of any significant changes in body weight. These results are discussed in relation to the kinds of adaptive feeding strategies that hamsters may utilize in their natural environment.     

囤积症的行为心理特征及相关因素

囤积症是指过度获取和不能丢弃那些没有用处或失去价值的物品。这种行为通常会给患者本人及其家庭成员带来感情、躯体、财务、社会甚至法律方面的负面影响。对于囤积症的行为特征、心理特征及相关因素,学界已有大量的研究。近期,囤积症已被纳入DSM-5,这将有助于确定有持续性丢弃困难的个体,并对其予以帮助与干预。     

Food-deprivation-induced behavioral arousal: mediation by hypothalamus and amygdala.

Electrolytic lesions of the basomedial hypothalamus eliminated food-deprivation-induced stabilimeter activity in rats that were prevented from becoming obese. Knife cuts lateral to the basomedial area (separating the medial and lateral hypothalamus) potentiated this activity, as did transections posterior to the basomedial region. Anterior transections (between anterior and medial hypothalamus), however, eliminated the effect. Lesions of the stria terminalis and amygdala likewise abolished deprivation-induced locomotor activity, but elevated ab-lib activity to a level comparable with that after deprivation in intact animals. Animals with combined basomedial-stria terminalis lesions behaved like animals with basomedial lesions. These results suggest that food-deprivation-induced locomotor activity in stabilimeter cages is due to a disinhibition of the basomedial hypothalamus by the amygdala via the stria terminalis.     

Hoarding behaviour and the defence of body weight in adult rats, following undernutrition during different periods of early development

In Experiment I, male rats, previously undernourished by underfeeding their mothers during lactation, weighed less as adults than progeny of mothers underfed during gestation, or than normally-nourished control rats. Daily 16 h food deprivation of the adults induced weight loss and elicited hoarding of food pellets. Deprivation-induced weight losses at criterion for hoarding did not differ significantly among the groups, and the critical weight at which hoarding began was thus significantly lower in the lactationally-undernourished group than in the controls. Thus adult rats, previously undernourished during their suckling period, appear to defend their body weights in a manner similar to controls, although at a lower level. Lactationally-undernourished rats also hoarded significantly fewer pellets than controls. Similar results were obtained when the rats were partially satiated before hoarding tests, suggesting that hoarding scores were unlikely to have been significantly affected by competition with feeding. Foetal undernutrition had weaker, and less consistent effects than lactational undernutrition on the ad libitum weight of the adult, and on the critical weight for hoarding. In Experiment II, severe undernutrition after weaning did not affect adult body weight, the weight loss necessary to induce hoarding, or the number of pellets hoarded. It is concluded that the pre-weaning period is specifically sensitive to the effects of undernutrition on body weight regulation and on hoarding. The data on hoarding do not support the view that a period of undernutrition at any time in early life increases the rat's responsiveness towards food.     

Control of-treadmill exercise of rats with hypothalamic stimulation

Running and resting behavior of rats was measured during treadmill exercise under conditions involving (1) rear-shock avoidance, (2) continuous electrical stimulation of the hypothalamus, or (3) no rear-shock and no hypothalamic stimulation. Hypothalamic stimulation was superior for eliciting consistent running with a minimum of resting. A second experiment demonstrated that decreases in hypothalamically elicited treadmill running resulting from prolonged exercise could be counteracted by increasing the intensity of the hypothalamic stimulus. A third experiment suggested that very little training was needed to induce a high and consistent level of running performance using hypothalamic stimulation.     

When hoarding is a symptom of OCD: A case series and implications for DSM-V

Hoarding, the excessive collection and failure to discard objects of apparently little value, can represent a serious psychiatric problem and pose a threat to public health. Hoarding has traditionally been considered a symptom (or symptom dimension) of Obsessive-Compulsive Disorder (OCD), but its nosological status has recently been debated. Mounting evidence suggests that, once other primary causes are ruled out, hoarding may be a discrete diagnostic entity, recently named Hoarding Disorder. However, hoarding can sometimes be a genuine OCD symptom. This can be confusing and clinicians may sometimes struggle making the differential diagnosis. To illustrate this, we describe 10 OCD patients with severe hoarding behavior that is better conceptualized as a symptom of OCD. We focus on the motivations for hoarding and the overlapping of hoarding with other obsessive-compulsive symptom dimensions. We estimate that this clinical presentation is relatively rare and accounts for a minority of severe hoarding cases. We discuss the unique characteristics of hoarding as a symptom of OCD and the implications for DSM-V.     

Conditioned and unconditioned fear organized in the periaqueductal gray are differentially sensitive to injections of muscimol into amygdaloid nuclei

The lateral and basolateral nuclei of the amygdala (LaA and BLA, respectively) serve as a filter for unconditioned and conditioned aversive information that ascends to higher structures from the brainstem, whereas the central nucleus of the amygdala (CeA) is considered to be the main output for the defense reaction. It has been shown that the dorsal periaqueductal gray (dPAG) is activated by threatening stimuli and has important functional links with the amygdala through two-way anatomical connections. In this work, we examined the influence of chemical inactivation of these nuclei of amygdala on the freezing and escape responses induced by electrical stimulation through electrodes implanted in the dPAG of Wistar rats. Each rat also bore a cannula implanted in the LaA, BLA or CeA for injections of muscimol (0.5 microg/0.5 microL) or its vehicle. The duration of freezing behavior that outlasts electrical stimulation of the dPAG was also measured. On the following day, these animals were submitted to a contextual fear-conditioning using foot shocks as unconditioned stimulus. Conditioned freezing to contextual cues previously associated with foot shocks was also inhibited by injections of muscimol into these amygdaloid nuclei. The contextual conditioned freezing behavior is generated in the neural circuits of conditioned fear in the amygdala. The data obtained also show that injections of muscimol into the three amygdaloid nuclei did not change the aversive threshold of freezing, but disrupted the dPAG post-stimulation freezing. Previous findings that the latter freezing results directly from dPAG stimulation and that it is not sensitive to a context shift suggest that it is unconditioned in nature. Thus, the amygdala can affect some, but not all, aspects of unconditioned freezing. Post-stimulation freezing may reflect the process of transferring aversive information from dPAG to higher brain structures.     

不同感觉功能对抑郁的影响及其神经机制

大脑通过视觉、听觉、嗅觉、味觉和触觉等感官通道接收来自外界的信息。不同感觉功能受损涉及抑郁发生的中枢机制,而基于不同感官通道进行适当刺激以及多感官联合干预也可能发挥显著的抑郁治疗作用。笔者以症状-脑区-机制-治疗为逻辑主线,首次系统梳理了五种主要感觉障碍人群的抑郁临床症状、抑郁神经机制以及基于感觉刺激的抗抑郁治疗。结果表明,不同感觉功能障碍对抑郁相关神经机制的影响可能表征了不同的抑郁病理,涉及神经元电活动(某些神经元放电和神经环路激活等)和神经生化改变(神经可塑性和神经发生、炎症免疫和HPA轴、神经激素和神经递质等),且主要发生在边缘系统及其附近脑区,涉及岛叶、颞叶、额叶等。因此,未来研究可聚焦于机体对不同感觉信息的提取,这将为人类抑郁的病因和治疗提供新的研究视角。     

Approach and withdrawal analysis of the effects of hypothalamic stimulation and lesions in rats.

In a paradigm in which rats would both initiate and terminate hypothalamic stimulation, "purely" rewarding lateral hypothalamic and "purely" aversive medial hypothalamic electrodes were identified. Subjects were then given a series of tests designed to assess the effects of brain stimulation on approach and withdrawal behaviors. Lateral hypothalamic stimulation facilitated approach behavior and suppressed withdrawal behaviors, whereas medial hypothalamic stimulation produced largely the opposite effects. No serious motor deficits due to stimulation were detected with either type of electrode. In a second experiment, the approach-withdrawal effects of bilateral lateral hypothalamic lesions were tested and found to suppress approach behaviors and facilitate withdrawal behaviors. Other neurological examinations revealed motor deficits, but these deficits do not account for the specific pattern of results observed on the approach-withdrawal tests. These approach-withdrawal phenomena are interpreted in terms of altering a natural balance between approach and withdrawl behavior facilitating systems in the lateral and medial hypothalamus, respectively.     

Long-term effects of preoptic area knife cuts on the maternal behavior of postpartum rats

Knife cuts severing the lateral connections of the medial preoptic area disrupt maternal behavior in postpartum rats. In these studies the knife cuts were produced 1-2 days prior to behavioral testing. The present study examined whether preoptic area knife cuts produce long-term deficits in maternal behavior. Nulliparous Charles River CD rats received knife cuts severing the lateral connections of the medial preoptic area or sham cuts. Approximately 2 weeks later they were mated. All females delivered young 22-23 days after mating, and litter size did not differ between the groups. Females with preoptic knife cuts cleaned their young, built nests (albeit of inferior quality), crouched over their young in a nursing posture, and lactated. The major deficit shown was the near total elimination of retrieval behavior. Females with preoptic knife cuts, however, were capable of performing the oral-motor responses associated with hoarding behavior. These results show that severing the lateral connections of the medial preoptic area does produce long-term deficits in maternal behavior, particularly with respect to maternal retrieving.     

An inexpensive electro-fistular swivel for negative feedback control of self-stimulation

A swivel was developed for concurrent intraorganismic fluid injection and intracranial electrical stimulation of the unrestrained rat. Effects of various intragastric injections on bar-pressing maintained by electrical stimulation of the hypothalamus were studied. In some subjects, intragastric injections of either water or milk decreased the rate of responding. This decrease resulted from pauses in responding rather than from decreases in the local rates of responding. The decrement in responding occurred at a lower gastric volume during milk injection than during water injection. In other subjects, however, neither water, milk, nor 32% sucrose injections affected the rate of self-stimulation.