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PubMed1996

Detection, discrimination and sensation of visceral stimuli.

Afferent visceral signals serve mostly regulatory functions and produce vague, diffuse body sensations, which are not well reflected in experimental paradigms requiring distinct and localized 'visceral perceptions'. A series of studies is summarized which compared behavioral discrimination of gastrointestinal distension stimuli with subjective sensation ratings in relation to basic perceptual operations such as detection, localization, graduation, and identification. Results showed that detection of gastrointestinal stimuli is possible without the subject's awareness (discrimination without reportable sensation). This process does not depend on stimulus intensity at volumes below those sufficient for subjective sensation. The latter is necessary, however, for intensity discrimination (graduation). Contrary to exteroception (e.g. vision), conscious subjective sensation is also required for stimulus localization. These differences in processing could not be explained by simple differences in response criteria. An intensity-dependent two-process model of gastrointestinal interoception is derived which differs from standard models of somatosensory information processing.

Adult↗

PubMed1991

Effect of repeated administrations upon cathinone discrimination and conditioned place preference.

1. Eight male rats were trained to discriminate the interoceptive cues produced by 0.8 mg/kg l-cathinone in a two-lever, food-motivated operant task and they were, subsequently, tested for preference to cathinone in a conditioned place preference (CPP)-test. 2. Once trained, the rats were placed on a 10 day regimen of twice-a-day non-contingent administrations of saline followed by a similar regimen of multiple injections of 0.8 mg/kg cathinone. 3. After each series of non-contingent administrations, the rats' ability to discriminate (0.2-0.8 mg/kg) cathinone, as well as their preference for it, was determined. 4. Results indicate that tolerance tends to develop to the effect of cathinone in its ability to control discriminative behavior as indicated by deficits in discriminative performance and a two-fold shift of the dose-response curve to the right. 5. In contrast, preference for cathinone, in the CPP-tests, was not significantly affected by the multiple cathinone administration regimen. 6. The possibility that tolerance to some behavioral effects may occur in habitual users of the cathinone-containing Khat shrub is discussed.

Alkaloids↗

PubMed1990

Reactivity to alcohol cues and induced moods in alcoholics.

It has been theorized that respondent conditioning processes in part underlie desire for alcohol and thus contribute to relapse after alcoholism treatment. One implication of this theory is that the relevant conditioned responses could be eliminated by respondent extinction, in which the alcoholic patient is exposed to alcohol-related stimuli while being prevented from consuming alcohol. However, exteroceptive cues such as the sight and smell of alcoholic beverages are not always sufficient to elicit desire for alcohol. In view of this, it has been suggested that interoceptive cues, such as mood states, may also play a role in eliciting desire for alcohol. To test this, eight alcoholic subjects were induced to experience negative or neutral moods on four separate days, and then exposed to the sight and smell of their favorite alcoholic drink, and to a neutral stimulus (seltzer water), in a within-subjects design. Results from this work indicate that: (a) negative moods can be reliably induced in the laboratory as confirmed by subjects' reports; (b) exposure to alcohol cues had no effect on desire for alcohol while subjects were in a relaxed, neutral mood state; (c) the presence of negative mood states alone appeared to be sufficient to elicit desire for alcohol in some subjects, regardless of whether alcohol or water was presented. These data argue that negative mood states may cue desire for alcohol independent of other cues. The data also suggest that reactivity to alcohol cues may be substantially reduced by relaxation.

Adult↗

PubMed1985

Selective attention and the brain: a hypothesis concerning the hippocampal--ventral striatal axis, the mediation of selective attention, and the pathogenesis of attentional disorders.

The mechanisms mediating selective attention are not currently known. Dysfunctional selective attention is a common and prominent finding in a variety of medical and psychiatric conditions. A hypothesis is developed that efferents from the hippocampal formation are the final common pathway of processes which determine the noteworthiness of both exteroceptive and interoceptive stimuli, and that dysfunction of these efferents is a common pathway for a variety of anatomical, electrophysiological, and neurochemical lesions. This hypothesis suggests that clinical syndromes of disordered attention may be caused by various lesions of efferent connections from hippocampal formation to nucleus accumbens. The hypothesis further addresses the possibility that the threshold of hippocampus to various classes of stimuli may change on a diurnal and phasic basis. Experimental evidence that bears on the hypothesis is reviewed and experimental implications of the hypothesis are explored.

Attention↗

PubMedDate not supplied

Organization of brainstem behavioral systems.

A review of recent literature suggests that the brainstem may play a more fundamental role in the elaboration of adaptive behaviors than has often been assumed. This view is indicated by current reports documenting the substantial behavioral repertoire of decerebrate animals and by the recent findings that electrical stimulation of localized areas in all major levels of the brainstem can induce complex and coordinated behaviors, including eating, grooming and attack. Indeed, behaviors elicited from sites in the caudal brainstem evidence unexpected goal specificity and stimulus control over response topography. Additional neuroanatomical and behavioral data are reviewed which further implicate caudal brainstem networks in process of reward and aversion. From these and other findings it is argued that integrating mechanisms for the expression of many aspects of species-characteristic behaviors are intrinsic to the brainstem. In line with this view, rostral hypothalamic-limbic mechanisms, while perhaps contributing refinement to the integration of behaviors, may best be viewed as phylogenetically newer control mechanisms making the expression of species-characteristic behaviors subordinate to additional class of exteroceptive and interoceptive stimuli.

Aggression↗

PubMedDate not supplied

Ethanol discrimination in Fawn-Hooded rats is compromised when compared to other strains.

The drug discrimination paradigm was used to evaluate the behavioral differences in response to ethanol between three strains of rats, viz., Sprague-Dawley, N/Nih and Fawn-Hooded. This latter group is thought to have a genetically-transmitted diminished central serotonin function. Each group of rats was trained to discriminate between the stimulus properties of 600 mg/kg ethanol and its vehicle in a two-lever, food-motivated operant task. Results indicate that the Fawn-Hooded rats required a significantly longer time and a higher ethanol dose to reach criterion discrimination performance. Furthermore, the ED50 value of the Fawn-Hooded rats, once trained, was higher than the Sprague-Dawley or N/Nih rats. The possibility that a reciprocal relationship exists between lowered central serotonin concentrations and higher alcohol consumption is suggested and the hypothesis that the diminished ability to recognize the interoceptive stimuli produced by ethanol may result in larger amounts of ethanol being consumed is offered.

Animals↗

PubMedDate not supplied

MDMA (Ecstasy) substitutes for the ethanol discriminative cue in HAD but not LAD rats.

Selectively bred high- and low-alcohol-drinking (HAD/LAD) rats were trained to discriminate the interoceptive stimuli produced by IP-administered 600 mg/kg ethanol (10% w/v in a two-lever, food-motivated operant task. Once criterion discrimination was attained, animals were tested with 3.0, 1.5, 1.0, and 0.5 mg/kg MDMA. Although no differences in alcohol discrimination were observed between the HAD and LAD animals, the HAD line was significantly more sensitive than the LAD line to the effects of MDMA. These results provide additional information to the growing body of evidence suggesting serotonergic mediation of some of the behavioral effects of ethanol.

Alcohol Drinking↗

PubMed1983

Hypothalamic pathways involved in metabolic regulatory functions, as identified by track-tracing methods.

The present review of the fiber connections of the hypothalamus has been concerned basically with recent data obtained by the aid of the autoradiographic and HRP tracer techniques. Evidence presented has shown that, besides confirming many of the older data, recent studies have resulted in the introduction of several conceptual modifications into the classic picture of hypothalamic hodological relationships. Among these conceptual modifications, the following can be mentioned: (1) the medially placed nuclei of the hypothalamus have a great number of long efferent and afferent connections with many extrahypothalamic structures; (2) many hypothalamic nuclei send direct projections to cell territories in the brainstem and spinal cord that contain preganglionic autonomic motor neurons; (3) several neural districts that lie caudal to the mesencephalon send direct projections to the hypothalamus; (4) in addition to the olfactory channel, other sensory pathways (including interoceptive and gustatory conduction lines) have a relatively direct access to hypothalamic mechanisms; (5) the hypothalamus sends fibers to several brainstem territories that give rise to widespread monoaminergic projections; and (6) there are anatomical pathways that establish reciprocal connections between the hypothalamus and the basal ganglia. Some of the possible physiological correlates of these anatomical findings in the context of metabolic regulatory functions have been briefly indicated.

Afferent Pathways↗

PubMed2005

Effects of 5,7-dihydroxytryptamine lesion of the dorsal raphe nucleus on ethanol discrimination in the rat.

It has been shown that ethanol produces a complex interoceptive cue in rodents with distinct GABAergic, glutamatergic, and serotonergic (5-hydroxytryptamine, 5-HT) components. The present study aimed to examine the contribution of the 5-HT system originating in the dorsal raphe nucleus (DRN) to the discriminative stimulus effects of ethanol in male Wistar rats. Therefore, selective lesions of 5-HT neurons in the DRN were induced by microinfusions of 5,7-dihydroxytryptamine. The DRN- and sham-lesioned rats were trained to discriminate ethanol (1.0 g/kg) from saline in a standard two-lever drug discrimination procedure. Acquisition of ethanol discrimination and discrimination performance after consumption of lower doses of ethanol did not differ between the groups. In substitution tests, diazepam (0.5-2.5 mg/kg), a nonselective benzodiazepine receptor agonist, partially generalized from the ethanol cue in both groups. In contrast, m-chlorophenylpiperazine (0.1-0.9 mg/kg), a mixed 5-HT(1B/2C) receptor agonist, did not mimic the ethanol cue. The drug decreased response rates in both groups, but this effect was more evident in the sham-lesioned group. A 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propyloamino)-tetraline (0.05-0.4 mg/kg), did not produce significant increase in ethanol-appropriate responding in either group. These results may indicate that 5-HT neurons of the DRN are not critically involved in ethanol discrimination in the rat.

5,7-Dihydroxytryptamine↗

PubMed2006

A putative role for cytokines in the impaired appetite in depression.

Impaired appetite and weight changes are commonly seen in patients with depression, but the pathophysiology behind this imbalance between energy intake and energy expenditure remains largely unknown. The aim of this paper is to review the literature regarding a possible role for cytokines in the regulation of appetite and body weight, with special emphasis on depression. There now exists a substantial amount of evidence that depressed patients show signs of immune activation including increased levels of proinflammatory cytokines. Cytokines, which by themselves have anorectic properties, stimulate the release of the cytokine-like anorexogenic peptide leptin. In addition to their anorectic properties, both proinflammatory cytokines and leptin interact with the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS) and the immune system. In turn, these systems regulate energy balance as well as they are dysfunctional in depression. Furthermore, both proinflammatory cytokines and leptin can induce anhedonia, one of the cardinal symptoms of depression. In view of the different effects on appetite and/or body weight observed in melancholic versus atypical depression, we suggest that cytokines are differentially altered in these subtypes of depression, and that this may explain some of the inconsistency in the reported findings of cytokine as well as leptin levels in depressed patients. Finally, we propose that the immune system uses the interoceptive pathway projecting to the insular cortex, a brain region where cytokine-induced changes in appetite could be partly mediated, and that this pathway is activated in depression.

Animals↗

PubMed2006

Nicotine does not produce state-dependent effects on learning in a Pavlovian appetitive goal tracking task with rats.

Past research has shown that when rats received 0.4mg base/kg nicotine paired reliably with intermittent sucrose delivery that anticipatory sucrose-seeking behavior (i.e., goal tracking) was differentially displayed in the nicotine state relative to intermixed saline sessions in which no sucrose was delivered. The present research extended this observation to a lower dose of nicotine (i.e., 0.2mg base/kg) and tested a state-dependent learning account of differential conditioned responding. According to this account, the increase in goal tracking on nicotine sessions reflects a chamber-sucrose association that is only recalled when in the nicotine state. We used a 2x2 factorial design in which rats received sucrose deliveries in one drug state (nicotine or saline) and were then tested in the same state (Nic-->Nic or Sal-->Sal) or a different state (Nic-->Sal or Sal-->Nic) after acquiring the conditioned response. A state-dependency account predicts disruption in conditioned goal tracking for rats that receive a shift in drug state on the test day. This disruption did not occur suggesting that differential control of conditioned responding by nicotine is more likely due to a direct excitatory association between the interoceptive cueing effects of nicotine and the appetitive qualities of sucrose.

Analysis of Variance↗

PubMed2006

Predicting eating disorder group membership: an examination and extension of the sociocultural model.

The purpose of this research was to examine and extend portions of the sociocultural model of bulimia nervosa (Stice, E. (1994). Review of the evidence for a sociocultural model of bulimia nervosa and an exploration of the mechanisms of action. Clinical Psychology Review, 14, 633-661; Stice, E., & Agras, W. S. (1998). Predicting onset and cessation of bulimic behaviors during adolescence: A longitudinal grouping analysis. Behavior Therapy, 29, 257-276). Participants were women who reported engaging in binge eating at baseline and the 1-year follow-up (n = 26), women who began binge eating between these 2 points (n = 25), and women who did not report binge eating during the course of the study (n = 199). Results of the first discriminant function analysis provided support for the sociocultural model. However, the results of subsequent analyses suggest that additional variables, including stress, escape-avoidance coping, and interoceptive awareness, emerged as important. Implications of these findings for our understanding of the development and maintenance of binge eating are discussed.

Adaptation, Psychological↗

PubMed2004

Anatomic evaluation of the orbitofrontal cortex in major depressive disorder.

BACKGROUND: The orbitofrontal cortex (OFC) plays a major role in neuropsychologic functioning including exteroceptive and interoceptive information coding, reward-guided behavior, impulse control, and mood regulation. This study examined the OFC and its subdivisions in patients with MDD and matched healthy control subjects. METHODS: Magnetic resonance imaging (MRI) was performed on 31 unmedicated MDD and 34 control subjects matched for age, gender, and race. Gray matter volumes of the OFC and its lateral and medial subdivisions were measured blindly. RESULTS: The MDD patients had smaller gray matter volumes in right medial [two-way analysis of covariance F(1,60) = 4.285; p =.043] and left lateral OFC [F(1,60) = 4.252; p =.044]. Left lateral OFC volume correlated negatively with age in patients but not in control subjects. Male, but not female patients exhibited smaller left and right medial OFC volumes compared with healthy control subjects of the same gender. CONCLUSIONS: These findings suggest that patients with MDD have reduced OFC gray matter volumes. Although this reduction might be important in understanding the pathophysiology of MDD, its functional and psychopathologic consequences are as yet unclear. Future studies examining the relationship between specific symptomatic dimensions of MDD and OFC volumes could be especially informative.

Adult↗

PubMed2006

Contextual and temporal modulation of extinction: behavioral and biological mechanisms.

Extinction depends, at least partly, on new learning that is specific to the context in which it is learned. Several behavioral phenomena (renewal, reinstatement, spontaneous recovery, and rapid reacquisition) suggest the importance of context in extinction. The present article reviews research on the behavioral and neurobiological mechanisms of contextual influences on extinction learning and retrieval. Contexts appear to select or retrieve the current relationship of the conditional stimulus (CS) with the unconditional stimulus (US), and they are provided by physical background cues, interoceptive drug cues, emotions, recent trials, and the passage of time. The current article pays particular attention to the effects of recent trials and trial spacing. Control of fear extinction by physical context involves interactions between the dorsal hippocampus and the lateral nucleus of the amygdala. This interaction may be mediated by gamma-aminobutyric acid (GABA)-ergic and adrenergic mechanisms.

Amygdala↗

PubMed2004

Paradoxical sleep deprivation potentiates amphetamine-induced behavioural sensitization by increasing its conditioned component.

The effects of paradoxical sleep deprivation (PSD-48 h) on the conditioned and unconditioned components of behavioural sensitization to amphetamine (two injections of 2.0 mg/kg, separated by 7 days) were studied using locomotion frequency of mice observed in an open-field as experimental parameter. Behavioural sensitization only occurred in PS deprived mice that were exposed to the open-field after the first amphetamine injection. The possible involvement of PSD in the development of a Pavlovian association between the stimulant effect of amphetamine and environmental as well as interoceptive drug cues is discussed.

Amphetamine↗

PubMed2006

Central glucagon like peptide-1 delays solid gastric emptying via central CRF and peripheral sympathetic pathway in rats.

It has been shown that glucagon like peptide-1 (GLP-1) acts on the central nervous system (CNS), in addition to its peripheral actions. Central administration of glucagon like peptide-1 (GLP-1) delays liquid gastric emptying via non-adrenergic, non-cholinergic neurons in rats. However, it remains unclear how central GLP-1 delays solid gastric emptying in rats. GLP-1 receptors at the CNS mediates the endocrine and anxiety responses to psychogenic and interoceptive stress. Corticotropin-releasing factor (CRF) is also known as a stress-related peptide, which delays gastric emptying of liquid and solid food via the autonomic nervous system. We have recently showed that central CRF delays solid gastric emptying via sympathetic pathways in rats. However, it remains unknown how central GLP-1 and CRF interact in mediating the inhibitory effect on solid gastric emptying. After a 24 h-fasting, GLP-1 was administered by intracisternal (ic)-injection immediately after the solid meal ingestion. Ninety minutes after the peptide injection, gastric contents were measured. Ic-injection of GLP-1 (30-3000 pmol) dose-dependently inhibited solid gastric emptying. Ic-injection of GLP-1 (3000 pmol)-induced delay of gastric emptying was partially antagonized by celiac ganglionectomy but not by atropine or N(G)-nitro-l-arginine methyl ester (L-NAME). Ic-injection of a CRF antagonist, astressin (2.8 nmol), partially antagonized GLP-1-induced delay of solid gastric emptying. These results indicate that central CRF and peripheral sympathetic pathway are, at least in part, involved in mediating central GLP-1-induced delay of solid gastric emptying in rats.

Animals↗

PubMed2006

The neurocognitive bases of human multimodal food perception: consciousness.

This review explores how we become aware of the (integrated) flavor of food. In recent years, progress has been made understanding the neural correlates of consciousness. Experimental and computational data have been largely based on the visual system. Contemporary neurobiological frameworks of consciousness are reviewed, concluding that neural reverberation among forward- and back-projecting neural ensembles across brain areas is a common theme. In an attempt to extrapolate these concepts to the oral-sensory and olfactory systems involved with multimodal flavor perception, the integration of the sensory information of which into a flavor gestalt has been reviewed elsewhere (Verhagen, J.V., Engelen, L., 2006. The neurocognitive bases of human multimodal food perception: Sensory integration. Neurosci. Biobehav. Rev. 30(5): 613_650), I reconceptualize the flavor-sensory system by integrating it into a larger neural system termed the Homeostatic Interoceptive System (HIS). This system consists of an oral (taste, oral touch, etc.) and non-oral part (non oral-thermosensation, pain, etc.) which are anatomically and functionally highly similar. Consistent with this new concept and with a large volume of experimental data, I propose that awareness of intraoral food is related to the concomitant reverberant self-sustained activation of a coalition of neuronal subsets in agranular insula and orbitofrontal cortex (affect, hedonics) and agranular insula and perirhinal cortex (food identity), as well as the amygdala (affect and identity) in humans. I further discuss the functional anatomy in relation essential nodes. These formulations are by necessity to some extent speculative.

Brain↗

PubMed2006

Responses to symptom induction exercises in panic disorder.

Exposure to panic symptoms (interoceptive exposure) is often included as part of treatment for panic disorder (PD), although little is known about the relative effects of particular symptom induction exercises. This study describes responses of individuals with PD and nonclinical controls to 13 standard symptom induction exercises and 3 control exercises. Generally, individuals with PD responded more strongly to symptom induction exercises than did controls. The exercises producing the most fear included spinning, hyperventilation, breathing through a straw, and using a tongue depressor. This study also reports findings regarding specific symptoms triggered by each exercise, the percentage of participants reporting fear during each exercise, and predictors of fear.

Adult↗