Biomedical subjects

K C Berridge

Publications and source records attributed to K C Berridge.

At least 37 records · Page 2Linked to original sources

PubMed1997

Haloperidol decreases hyperkinetic paw treading induced by globus pallidus lesions in the rat.

Systemic haloperidol injections decrease the severity of several hyperkinetic syndromes caused by damage to the basal ganglia in humans. A model of hyperkinesia in the rat, exaggerated paw treading triggered by oral sensory stimulation, has been reported previously to result from lesions of the globus pallidus or ventral pallidum/substantia innominata. This hyperkinesia appears as forepaw and forelimb extension and retraction, which can be emitted vigorously and repeatedly for up to minutes at a time. The present study aimed to discover whether this experimental hyperkinesia is pharmacologically similar to human hyperkinetic syndromes: can it be suppressed by neuroleptic administration? Systemic injections of haloperidol (2 mg/kg), diazepam (5 mg/kg, as a sedative comparison), or vehicle were given to rats that expressed the paw treading syndrome after pallidal lesions. Effects on hyperkinetic treading and on tests of sensorimotor function were compared. Results indicated that haloperidol was effective in ameliorating the hyperkinesia in rats with bilateral globus pallidus lesions but not in rats with ventral pallidum/substantia innominata lesions. By contrast, diazepam, which produced sedation and sensorimotor impairment, did not decrease the hyperkinesia induced by either lesion. Although only haloperidol decreased hyperkinetic treading after globus pallidus lesions, haloperidol produced less of a sensorimotor impairment than diazepam on climbing, hanging, and righting reflex tests. These results implicate a specific role for dopamine neurotransmission in the expression of triggered hyperkinetic treading induced by globus pallidus lesions.

Animals↗

PubMed1997

Pimozide does not shift palatability: separation of anhedonia from sensorimotor suppression by taste reactivity.

Several "taste reactivity" studies of dopamine and reward have concluded that pimozide suppresses the hedonic reaction patterns normally elicited by sucrose but enhances aversive reaction patterns elicited by quinine. However, other taste reactivity studies have failed to find hedonic/aversive shifts in reaction patterns after dopamine antagonists or dopamine lesions. The divergent conclusions have come from two different laboratories. To resolve the controversy regarding dopamine blockade and palatability, the present study joined the two laboratories to investigate the effect of pimozide on taste reactivity patterns elicited by sucrose and quinine. The results replicated many (but not all) of the earlier findings and identified procedural factors responsible for different outcomes. Overall, the results provide evidence for sensorimotor effects of pimozide on taste reactivity but not for a hedonic shift in palatability. Pimozide suppressed both hedonic and aversive reaction patterns in a gradual sensorimotor fashion when the eliciting taste stimulus was repeated or continued for several minutes. The general suppression typically did not alter the initial reaction to a taste but emerged only after an oral infusion of sucrose or quinine continued for several minutes or trials. Aversive reactions were never enhanced. The balance between hedonic and aversive reaction patterns was not shifted by pimozide. We conclude that pimozide produces a sensorimotor impairment of taste reactivity patterns but does not shift taste palatability toward anhedonia or aversion.

Animals↗

PubMed1996

Brainstem mediates diazepam enhancement of palatability and feeding: microinjections into fourth ventricle versus lateral ventricle.

The hypothesis that benzodiazepine-induced hyperphagia is due to a specific enhancement of the palatability of foods has been supported by previous 'taste reactivity' studies of affective (hedonic and aversive) reactions to taste palatability. Diazepam and chlordiazepoxide enhance hedonic reactions of rats (rhythmic tongue protrusions, etc.) to sweet tastes in a receptor-specific fashion. A role for brainstem circuits has been indicated by a previous demonstration of the persistence of the taste reactivity enhancement by diazepam after midbrain decerebration. The present study examined whether benzodiazepine brainstem receptors are the chief substrates for palatability enhancement even in intact brains. We compared the effectiveness of benzodiazepine microinjections to elicit feeding and enhance hedonic reactions when delivered into either the lateral ventricle (forebrain) or the fourth ventricle (brainstem) of rats. The results show diazepam is reliably more effective at eliciting feeding and enhancing positive hedonic reactions to oral sucrose when microinjections are made in the fourth ventricle than in the lateral ventricle. We conclude that brainstem neural systems containing benzodiazepine-GABA receptors are likely to be the chief substrates for benzodiazepine-induced palatability enhancement.

Animals↗

PubMed1996

Implementation of action sequences by a neostriatal site: a lesion mapping study of grooming syntax.

The neostriatum and its connections control the sequential organization of action ("action syntax") as well as simpler aspects of movement. This study focused on sequential organization of rodent grooming. Grooming syntax provides an opportunity to study how neural systems coordinate natural patterns of serial order. The most stereotyped of these grooming patterns, a "syntactic chain," has a particularly stereotyped order that recurs thousands of times more often than could occur by chance. The purpose of the present study was to identify the crucial site within the striatopallidal system where lesions disrupt the syntax or serial order of syntactic grooming chains without disrupting constituent movements. Small excitotoxin lesions were made using quinolinic acid at bilateral sites within the dorsolateral, dorsomedial, ventrolateral, or ventromedial neostriatum, or in the ventral pallidum or globus pallidus of rats. An objective technique for mapping functional lesions was used to quantify cell death and to map precisely those lesions that disrupted grooming syntax. Our results identified a single site within the anterior dorsolateral neostriatum, slightly more than a cubic millimeter in size (1.3 x 1.0 x 1.0 mm), as crucial to grooming syntax. Damage to this site did not disrupt the ability to emit grooming actions. By contrast, damage to sites in the ventral pallidum and globus pallidus impaired grooming actions but left the sequential organization of grooming syntax intact. Neural circuits within this crucial "action syntax site" seem to implement sequential patterns of behavior as a specific function.

Animals↗

PubMed1996

Food reward: brain substrates of wanting and liking.

What are the neural substrates of food reward? Are reward and pleasure identical? Can taste pleasure be assessed in animals? Is reward necessarily conscious? These questions have re-emerged in recent years, and there is now sufficient evidence to prompt re-examination of many preconceptions concerning reward and its relation to brain systems. This paper reviews evidence from many sources regarding both the psychological structure of food reward and the neural systems that mediate it. Special attention is paid to recent evidence from "tasty reactivity" studies of affective reactions to food. I argue that this evidence suggests the following surprising possibilities regarding the functional components and brain substrates of food reward. (1) Reward contains distinguishable psychological or functional components--"liking" (pleasure/palatability) and "wanting" (appetite/incentive motivation). These can be manipulated and measured separately. (2) Liking and wanting have separable neural substrates. Mediation of liking related to food reward involves neurotransmitter systems such as opioid and GABA/benzodiazepine systems, and anatomical structures such as ventral pallidum and brainstem primary gustatory relays. Mediation of wanting related to food reward involves mesotelencephalic dopamine systems, and divisions of nucleus accumbens and amygdala. Both liking and wanting arise from vastly distributed neural systems, but the two systems are separable. (3) Neural processing of food reward is not confined to the limbic forebrain. Aspects of food reward begin to be processed in the brainstem. A neural manipulation can enhance reward or produce aversion but no single lesion or transection is likely abolish all properties of food reward. (4) Both wanting and liking can exist without subjective awareness. Conscious experience can distort or blur the underlying reward process that gave rise to it. Subjective reports may contain false assessments of underlying processes, or even fail at all to register important reward processes. The core processes of liking and wanting that constitute reward are distinct from the subjective report or conscious awareness of those processes.

Behavior↗

PubMed1995

Benzodiazepines, appetite, and taste palatability.

Benzodiazepine agonists stimulate feeding in animals. This paper reviews evidence which indicates that benzodiazepine-induced feeding is due to a specific enhancement of the perceived palatability of food and fluids, and is not a mere secondary consequence of anxiety reduction. In studies of the effect of benzodiazepines on affective reactions that are naturally elicited from rats by tastes, we have shown that (a) benzodiazepines enhance hedonic taste palatability in a receptor-specific fashion; (b) the relevant receptors and the minimal neural circuitry required to mediate benzodiazepine-induced palatability enhancement both exist complete in the decerebrate brain stem; and (c) even in normal brains, receptors in the brain stem, not forebrain, are the primary substrate for the benzodiazepine-induced enhancement of taste palatability. We conclude that a 'benzodiazepine-GABA' neural system in the brain stem constitutes an important component of the neural hierarchy responsible for taste pleasure. The reason why benzodiazepine tranquilizers have not been reported to enhance palatability for humans may be that the appropriate studies have not yet been done, that human doses are low, and that the brain stem palatability system is less responsive to commonly prescribed agonists that are anxiety/arousal benzodiazepine systems. Finally, in keeping with the purpose of the symposium in which this paper was originally presented, we discuss a number of issues regarding the measurement and interpretation of taste reactivity data.

Animals↗

PubMed1995

Central enhancement of taste pleasure by intraventricular morphine.

Do centrally-administered opioid agonists stimulate feeding by enhancing the palatability of foods? This hypothesis has been supported by several lines of evidence, including previous 'taste reactivity' studies of the influence of systemic morphine on affective (hedonic and aversive) behavioral reactions to taste palatability. The presents study examined whether opioid agonists enhance palatability by acting centrally on brain palatability systems. Here we report the effect of intraventricular microinjections of morphine (0, 12, 25, 50 nmols) on hedonic taste reactions to a 0.12 M sucrose solution. The effect on feeding was also assessed in order to determine whether feeding and palatability enhancement are linked, as would be required by the hypothesis that feeding is due to enhanced palatability. Both hedonic taste reactivity patterns and feeding were significantly increased together by morphine administration into the lateral ventricle. We conclude that opioid-induced enhancement of the hedonic palatability of food is a centrally mediated effect. Enhancement of food palatability may be an important psychological route by which intracranial administration of opioid agonists induce feeding.

Animals↗

PubMed1994

Mapping of globus pallidus and ventral pallidum lesions that produce hyperkinetic treading.

The purpose of this study was to identify sites where striatopallidal lesions produce two distinct sensory-triggered hyperkinetic syndromes: (1) exaggerated forelimb treading alone to oral taste infusions and (2) sensorimotor exaggerated treading plus enhanced aversive reactions to taste infusions. The behavioral characteristics of these syndromes have been described previously (Berridge, K.C. and Cromwell, H.C., Behav. Neurosci., 104 (1990) 778-795). Bilateral excitotoxin lesions were made using quinolinic acid (10 micrograms in 1 microliter) in the caudate/putamen, nucleus accumbens, globus pallidus or ventral pallidum/substantia innominata. In order to identify the precise center, borders, severity and size of lesion sites that caused these hyperkinetic treading syndromes, neuron counts (modified fractionator technique) and glial fibrillary acidic protein immunoreactivity (GFAP-IR) densitometry were used in a stereological mapping analysis. The site of lesions that produced the hyperkinetic treading syndrome without enhanced aversion was found to be restricted to the globus pallidus (GP). Damage exceeding 60% neuron loss bilaterally within a 0.8 x 1.0 x 1.0 mm subregion of the ventromedial GP produced this syndrome. The site of lesions that produced the combined syndrome of hyperkinetic treading and aversive enhancement was ventral to the globus pallidus, within the ventral pallidum/substantia innominata (VP/SI). Damage exceeding 70% neuron loss bilaterally within a 1.0 x 0.5 x 1.0 mm diameter subregion of the ventromedial ventral pallidum/substantia innominata produced this syndrome. This subterritory was located immediately lateral to the border of the lateral hypothalamus. Bilateral lesions to the caudate/putamen or nucleus accumbens did not produce either hyperkinetic treading syndrome. These results are discussed in terms of the connectivity of the ventral pallidal/substantia innominata and globus pallidus regions and in terms of neuropathological models of hyperkinetic disorders.

Animals↗

PubMed1993

Lesions of the central nucleus of the amygdala. I: Effects on taste reactivity, taste aversion learning and sodium appetite.

Bilateral damage to the central nucleus of the amygdala (CeAX) in the rat blunts need-induced NaCl intake and abolishes daily need-free NaCl intake when measured with a two-bottle test. Such a deficit could be the result of impaired taste function. To assess the taste function of the CeAX rat various taste stimuli were introduced directly into the oral cavity and taste-elicited oral motor responses were measured. Oral motor responses elicited by 0.62 M and 0.13 M sodium chloride, 0.3 M sucrose and 0.01 M citric acid, were similar in control and CeAX rats. Additionally CeAX and control rats acquired a taste aversion for fructose or maltose when either was paired with LiCl. Finally, in CeAX rats, like in control rats, the pattern of oral motor responses to 0.5 M NaCl was dependent on internal state; sodium depletion dramatically altered taste-elicited oral motor behavior. These results suggest that, in the rat, the deficits in NaCl intake behavior that follow CeAX do not appear to be a result of dramatic changes in gustatory function.

Amygdala↗

PubMed1993

Where does damage lead to enhanced food aversion: the ventral pallidum/substantia innominata or lateral hypothalamus?

It is well known that lesions of the lateral hypothalamus (LH) produce aphagia. Several previous studies have reported that lateral hypothalamus damage produces food aversion in addition to aphagia. However, damage to other regions near the LH also produce aphagia and enhanced aversion. The purpose of this study was to resolve where the site or sites for aversion-inducing lesions is/are located. Small, bilateral excitotoxin lesions (QUIN, 10 micrograms in 1 microliter or IBO, 15 micrograms in 1 microliter) or bilateral sham injections of vehicle were made into the globus pallidus (GP), the ventral pallidum/substantia innominata (VP/SI) or the lateral hypothalamus (LH). Affective reactions to taste were elicited by infusing sucrose solutions (1 M) into the mouth via chronic oral cannulae. The number of aversive responses (gapes, chin-rubbing, head-shaking and forelimb flails) emitted was tallied. Individual lesions were mapped and a single 'necessary and sufficient' site for damage-induced aversion was identified (the area of overlapping damage common to all rats that showed enhanced aversive reactions). To identify the lesions, two lesion-mapping techniques were used: (1) a conventional neuron-counting procedure in which an attempt is made to count all neurons within a brain region, and (2) a new modified 'fractionator' procedure consisting of exhaustive 400 x magnification counts at point locations within a brain region. Results indicated that aversive reactions to food are enhanced only following bilateral neuron loss (> 70%) from the caudal ventromedial VP/SI alone. This shared site has a lateral diameter of 1.0 mm, a dorsoventral diameter of 0.5 mm and a rostrocaudal diameter of 1.0 mm. Damage restricted to the LH never produced enhanced aversion even when it produced aphagia. The crucial region for aversion is located ventral and medial to the globus pallidus and dorsal and lateral to the lateral hypothalamus.

Animals↗

PubMed1993

Pleasantness of a sweet taste during hunger and satiety: effects of gender and "sweet tooth".

Hungry or sated adult female (N = 29) and male subjects (N = 28), classified according to whether they had eaten or not within 2 h, rated four concentrations of sucrose in a lime drink for their sweetness intensity and pleasantness. Subjects also rated their attitude towards sweets in general (self-reported sweet tooth). Female subjects rated the solutions as less pleasant when tasted soon after a meal. Male subjects showed a non-significant trend in the same direction. Female subjects also rated the solutions as more intense than the male subjects did. Moreover, subjects who reported having a "sweet tooth" (regardless of gender) showed a significant alliesthesia effect (i.e., enhancement of pleasantness of sweet tastes by hunger), whereas those with "no sweet tooth" did not. We conclude that both gender and the degree of individual "sweet tooth" influence alliesthesia.

Adult↗

PubMed1993

Morphine enhances hedonic taste palatability in rats.

The question of whether opiates stimulate feeding by enhancing taste pleasure was investigated by examining the effect of morphine upon hedonic and aversive reactions to taste (tongue protrusions, gapes, etc.). Rats (n = 12) were given SC injections of morphine (4 mg/kg) or equal volumes of isotonic saline 2 h after the start of their daily light cycle. Food intake was measured in a 2-h test. On days when they were given morphine, rats ate significantly more food than when given saline. Hedonic and aversive taste reactions were elicited by an infusion of sucrose-quinine solution into the mouth and were measured subsequently in a slow-motion video analysis. The same rats that showed an increase in food intake after treatment with morphine showed a significant increase in their positive hedonic responses. Aversive reactions were unchanged by morphine. The results support the hypothesis that morphine enhances feeding by increasing the hedonic palatability of food.

Animals↗

PubMed1992

Cortex, striatum and cerebellum: control of serial order in a grooming sequence.

Rats emit grooming actions in sequences that follow characteristic patterns of serial order. One of these patterns, a syntactic chain, has a particularly stereotyped order that recurs spontaneously during grooming thousands of times more often than could occur by chance. Previous studies have shown that performance of this sequence is impaired by excitotoxin lesions of the corpus striatum. In this study we examined whether the striatum is unique in its importance to this behavioral sequence or whether control of the sequence instead depends equally upon the cortex and cerebellum. In two experiments, a fine-grained behavioral analysis compared the effects of striatal ablation to the effects of motor cortex ablation, ablation of the entire neocortex, or ablation of the cerebellum. Cortical and cerebellar aspiration produced mere temporary deficits in grooming sequences, which appeared to reflect a general factor that was nonsequential in nature. Only striatal damage produced a permanent sequential deficit in the coordination of this syntactic grooming chain. We conclude that the striatum has a unique role in the control of behavioral serial order. This striatal role may be related to a number of sequential disorders observed in human diseases involving the striatum.

Animals↗

PubMed1991

Modulation of taste affect by hunger, caloric satiety, and sensory-specific satiety in the rat.

Human judgements of the pleasure of sweetness have been reported to be modulated by caloric hunger, satiety, and sensory-specific satiety. This study examined both hedonic and aversive facial/somatic reactions to taste in the rat, in order to confirm the relation of hunger and satiety to taste affect, and to assess whether affective modulation depends upon the cognitive factors that mediate human self-interpretation of affect. In the first experiment, the affective reactions of rats to sweet, bittersweet, and water tastes were assessed in five states of caloric hunger or satiety. Caloric satiety reduced positive hedonic reactions below normal levels. Conversely, 48-h food deprivation (but not 24-h deprivation) increased hedonic reactivity. Hedonic enhancement by hunger was not restricted to sweet tastes, but also extended to the palatability of water. Only the hedonic reactions to taste were changed by hunger or satiety: taste aversion was not altered. The second experiment compared the magnitude of affective change during sensory-specific satiety and caloric satiety. Taste-reactivity elicited by sucrose solution or milk was assessed after satiating meals of each of those foods. Sensory-specific satiety further reduced hedonic reactions below the level achieved by caloric satiety alone. Both for caloric satiety and for sensory-specific satiety changes in affect were restricted to positive hedonic reactions: no increase in aversion accompanied the hedonic decrements. These results confirm that taste affect is modulated during caloric hunger, caloric satiety, and sensory-specific satiety. In addition they indicate that the modulation of taste affect by hunger and satiety is confined to the positive limb of the two dimensions (hedonic vs. aversive) of palatability.

Affect↗

PubMed1991

What psychological process mediates feeding evoked by electrical stimulation of the lateral hypothalamus?

Because electrical stimulation of the lateral hypothalamus (ESLH) can elicit both feeding and reward, most investigators have concluded that stimulation does not evoke the aversive cues associated with hunger. It has been hypothesized, instead, that ESLH primes ingestion by evoking pleasurable taste sensations. A direct taste of this hedonic hypothesis was undertaken in rats that showed stimulus-bound feeding. Contrary to the prediction, it was found that the taste reactions (gapes, tongue protrusions, etc.) during ESLH were more aversive than hedonic. It is suggested that the stimulation influences behavior by potentiating the salience, but not the hedonic value, of external stimuli. The advantages of this incentive salience hypothesis are that it circumvents the need to postulate a hedonic sensory experience during stimulation and that it can explain how evoked feeding may switch to other behaviors when conditions are altered.

Animals↗

PubMed1990

A comparison of benzodiazepine, serotonin, and dopamine agents in the taste-reactivity paradigm.

Previous studies have shown that rats' positive, palatability-dependent consummatory reactions to infused tastes are selectively facilitated by a benzodiazepine agonist (chlordiazepoxide), and that this effect can be blocked by the coadministration of benzodiazepine antagonists (e.g., Ro 15-1788). The purpose of the present study was to determine whether agents acting at other receptor sites (dopaminergic, serotonergic), which have been shown to modulate food consumption, might also modify rats' palatability-dependent reactivity to infused tastes. In this experiment, the benzodiazepine agonist, diazepam, facilitated positive palatability reactions, while dopaminergic agents (haloperidol, apomorphine, amphetamine) had no significant effects on either positive or aversive reactions. The putative 5-HT1A agonists, buspirone and gepirone, had a general inhibitory action on both positive and aversive palatability reactions. These results are surprising in view of the effects of serotonergic and dopaminergic agents on food and fluid intake. Our results suggest that the benzodiazepine receptor system may play a special role in the neural control of appetite through its enhancement of the positive palatability of tastes. Dopamine systems, by contrast, appear to control food intake by modulating processes that are independent of food affect evaluation.

Amphetamine↗

PubMed1990

Motivational-sensorimotor interaction controls aphagia and exaggerated treading after striatopallidal lesions.

This study examined the relationship between sensorimotor and motivational functions of the corpus striatum. In rats, excitotoxic lesions of the corpus striatum (neostriatum and globus pallidus) caused by kainic or quisqualic acid can produce both aversive aphagia and a "choreic" sensorimotor syndrome: an exaggerated treading of the forepaws that is triggered by oral sensory stimulation. Experiment 1 used a recovery-of-function approach to show that (a) aphagia induced by ventroposterior striatopallidal lesions was accompanied by an enhancement of aversion (a specific motivational process) to sweet stimuli, which was expressed in taste reactivity measures of affective evaluation; (b) aphagia and enhanced aversion recovered together; and (c) exaggerated treading did not disappear with aphagia-aversion but narrowed the range of its eliciting trigger to sour and bitter stimuli. Experiment 2 used a partial lesion approach to show that this dissociation of enhanced aversion and exaggerated treading could be reproduced by smaller lesions immediately after striatopallidal damage. Experiment 3 used a conditioned aversion procedure to show that the stimulus for exaggerated treading was aversion (natural or conditioned) and not a simple sensory feature of oral stimulation. Three conclusions were made: (a) Exaggerated treading after a small lesion or after partial recovery from a larger one results from a restructuring of a sensorimotor relations that is nested within a system of aversive reaction, (b) exaggerated treading is elicited only by tastes that elicit natural or conditioned aversion, and (c) more extensive lesions potentiate aversion to tastes that are normally palatable and expand the range of treading elicitors to include those tastes. In other words, affective and sensorimotor systems interact in a hierarchial manner in the production of choreic treading. These results demonstrate a specific hierarchical link between motivational and sensorimotor functions mediated by striatopallidal circuits.

Affect↗

PubMed1989

Progressive degradation of serial grooming chains by descending decerebration.

Rule-governed behavioral chains occur predictably within the grooming sequences of rats. Descending levels of decerebration were used to identify the minimum brain substrate needed to generate the sequential structure of a chain that connects up to 25 actions into a stereotyped grooming pattern. Full brain transections in the coronal plane isolated the decerebrate brainstem of rats at one of 3 different levels: mesencephalic (above the midbrain), metencephalic (above the hindbrain), and myelencephalic (above the medulla oblongata). Complete chain sequences were produced successfully by higher decerebrates, demonstrating that brainstem circuitry suffices for the basic generation of this sequential pattern. The pattern of sequential degradation across lower transection levels was gradual and continuous, raising the possibility that the generating circuitry for this chain may not be localized at a single level within the brainstem but rather may be distributed across the hindbrain as a degenerate or parallel network. The competence of this network appears to be reduced merely in increments by descending transections. This possibility is compared to localized generator alternatives.

Animals↗