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PubMed2002

Evidence for an auditory subsector within the zona incerta of rats.

This study explores the patterns of connections between the zona incerta (ZI) of the thalamus and the major auditory centres of the rat brain. Two series of experiments were performed using neuroanatomical tract tracing methods (biotinylated dextran or cholera toxin subunit b). First, tracers were injected into the ZI and resultant patterns of labelling in the auditory centres were examined. Labelling was seen in distinct subdivisions of the temporal cortex (Te3), medial geniculate complex (medial division; MGm), inferior colliculus (external cortex; ICe) and cochlear nucleus (dorsal and ventral divisions). For the most part, these subdivisions are involved in more associative or integrative aspects of audition. In a second series of experiments, three of these centres (Te3, ICe, cochlear nucleus) were injected with tracers and the labelling patterns formed in the ZI were explored. These results show that each of these connections makes a very distinct territory or subsector within the most lateral region of the ZI. This subsector of connectivity with the auditory centres does not respect the well defined cytoarchitectonic sectors of ZI, being made up of small slabs in both the dorsal and ventral sectors. Overall, the results suggest that ZI may integrate auditory information together with the other exteroceptive and interoceptive information that it receives and then influences subsequently global states of arousal and/or attention.

Animals↗

PubMed2002

[Physiology and pathophysiology of visceral pain].

Visceral pain is diffusely localized, referred to deep somatic tissues, skin and viscera, frequently not correlated with an actual trauma, commonly correlated with strong negative affective reactions and accompanied by strong protective autonomic and motor reactions. It is correlated with the excitation of spinal (thoraco-lumbar, sacral) visceral afferents and (with a few exceptions) not with the excitation of vagal afferents. Spinal visceral afferents are polymodal and can be excited by physical and chemical stimuli. All groups of visceral afferents can be sensitized (e.g.by inflammation). Normally silent (mechanically insensitive) visceral afferents are recruited by inflammation. Individual visceral afferent neurons project in laminae I and V of the dorsal horn over several segments, medio-lateral over the entire width of the dorsal horn and to the contralateral side. Their activity is synaptically transmitted, in these and deeper laminae, to viscero-somatic convergent neurons which receive additional afferent synaptic input from skin and deep somatic tissues of the corresponding dermatomes,myotomes and sclerotomes. The mechanism of sensitization of viscerosomatic convergent neurons (central sensitization) during sensitization of spinal visceral afferents is unclear.Viscero-somatic tract neurons project to lower and upper brain stem,hypothalamus and via the thalamus to various cortex areas. Visceral nociception and pain is presumably (together with other visceral sensations and homeostatic regulations of autonomic body functions) primarily represented in the insula in the context of interoception. The insula obtains its main peripheral afferent input from lamina I neurons via the Nucleus ventromedialis posterior of the thalamus. The transmission of visceral impulses in the spinal cord is modulated by the endogenous control systems in the brain stem which are in turn under the control of cortex and limbic system.

Afferent Pathways↗

PubMed2006

Sensory innervation of the brain (primary interoceptor neurons of the brain and their asynaptic dendrites).

Published data and our own studies on the sensory innervation of the brain are summarized. Primary interoceptive sensory neurons were analyzed: brain neurons bearing cilia; supraependymal plexuses and intraependymal neurons in contact with the cerebrospinal fluid; Cajal-Retzius neurons in the boundary layer of the cerebral cortex; Dolgo-Saburov paravasal neurons in the brain and spinal cord; Lugaro cells in the cerebellum; and various synaptically NO-positive neurons in the cerebral cortex, whose asynaptic dendrites innervate the precapillary space. Consideration of the lack of pain sensitivity of the brain and the parenchymatous tissues of the internal organs, which contain local primary sensory neurons similar to intramural metasympathetic sensory neurons of Dogel type II, led to the hypothesis that brain and other intraorgan tissue receptors are involved in short "autonomic" reflex arcs controlling only local metabolism but not pain reactions.

Brain↗

PubMed1989

Bulimia nervosa and dietary restraint.

Patients with bulimia nervosa were compared with non-bulimic restrained and unrestrained eaters on several questionnaire and interview measures related to eating patterns, preoccupation with dieting and food, and general psychopathology. Bulimic subjects did not differ significantly from non-bulimic restrained eaters on measures of fear of weight gain, dietary restraint, and the Eating Disorders Inventory (EDI) subscales of Drive for Thinness and Body Dissatisfaction, although both groups scored significantly higher on these measures than unrestrained eaters. Subjects with bulimia nervosa differed significantly from both restrained and unrestrained eaters on the Eating Habits Checklist, the Beck Depression Inventory, the EDI total score and Interoceptive Awareness, Introversion and Bulimia subscales, the Three Factor Eating Questionnaire (TFEQ), Disinhibition subscale and the Symptom Checklist 90-revised version. These findings show that bulimic patients may be quite similar to their restrained, non-bulimic counterparts on dietary concern and ideals of slenderness and suggest the importance of including a restrained control group in attempts to isolate the variables that differentiate individuals with the clinical eating disorder from their peers who demonstrate normative discontent about body weight and shape.

Adult↗

PubMed1990

Waning of panic sensations during prolonged hyperventilation.

Recent theories about panic emphasize that a hyperventilatory positive feedback loop is involved in panic: catastrophic misinterpretation of bodily sensations may trigger anxiety, anxiety may stimulate hyperventilation, hyperventilation may promote the salience of feared sensations etc. Such models leave unexplained how and when panics come to an end. It was hypothesised that panic with hyperventilation may end because pronounced hyperventilation becomes, in the course of time, less powerful in generating perceivable bodily sensations. Twenty healthy subjects hyperventilated forcefully and experienced clear panic symptoms as defined by DSM IIIR. When pCO2 was kept 55% below base line for 90 min, panic symptoms waned. The mean intensity of the symptoms declined as did the number of symptoms occurring. No panic symptoms were observed in the control group (n = 20) who ventilated normally. In so far as hyperventilation is involved in the positive feedback loops that characterize panic, panic attacks may be time-limited because sensations induced by hyperventilation become less salient even if massive hyperventilation continues. As to the explanation of the reported phenomenon, it is suggested that, apart from habituation, local physiological changes due to prolonged hyperventilation may produce a decrease in interoceptive input.

Adult↗

PubMed1993

Group cognitive-behavioral treatment of panic disorder.

The present study examined the efficacy of an 8-wk, cognitive-behavioral group treatment for panic disorder. Patients meeting DSM-III-R criteria for panic disorder with or without agoraphobia were randomly assigned to treatment (N = 34) or delayed treatment control (N = 33). The treatment consisted of: (a) education and corrective information; (b) cognitive therapy; (c) training in diaphragmatic breathing; and (d) interoceptive exposure. At posttreatment, 85% of treated Ss were panic free, compared to 30% of controls. Treated Ss also showed clinically significant improvement on indices of anxiety, agoraphobia, depression and fear of fear. Recovery, as estimated conservatively by the attainment of normal levels of functioning on each of the major clinical dimensions of the disorder (i.e. panic, anxiety and avoidance), was achieved in 64% of the treated Ss and 9% of the controls. At the 6 month follow-up, 63% of the treated patients met criteria for recovery. These findings mirror those from recently-completed trials of individually-administered cognitive-behavioral treatment, and suggest that CBT is a viable alternative to pharmacotherapy in the treatment of panic disorder.

Adult↗

PubMed1977

Effects of vagal volleys on units of intralaminar and juxtalaminar thalamic nuclei in monkeys.

As part of an attempt to clarify the nature of inputs to the limbic cortex, the thalamic intralaminar and juxtalaminar nuclei were explored for unit responses to vagal volleys in awake, sitting squirrel monkeys. Vagal shocks elicited responses of a large percentage of units in the anterior medial, paracentral, lateral dorsal, and lateral, and medial dorsal nuclei, as well as in part of the ventral lateral nucleus adjacent to the paracentral. Responsive units showed either initial excitation or initial inhibition. As in the preceding study on the cingulate and supracingulate cortex, there were two main types of initially excited units: type 1 responded with a discharge of 1-3 spikes at relatively short and constant latencies, while type 2 units were characterized by a burst of 3-14 spikes at longer and more variable latencies. Although the findings were compatible with the hypothesis that the anterior and paracentral nuclei transmit vagal impulses to the cingulate and supracingulate cortex, an analysis of latencies suggested that a more rapidly conducting pathway(s) accounts for latencies as short as 12 msec of some cingulate units. Twenty-eight percent of 367 units in the medial dorsal nucleus responded to vagal volleys. This finding gives substantial support to the traditional view that the medial dorsal nucleus transmits interoceptive information to limbic and neocortical areas of the orbitofrontal region.

Afferent Pathways↗

PubMed1978

Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat.

Ascending projections from the caudal (general-visceroceptive) part of the nucleus of the solitary tract (NTS) were studied experimentally in the rat by the aid of the anterograde autoradiographic and the retrograde horseradish peroxidase (HRP) tracer techniques. Microelectrophoretic deposits of tritiated proline and leucine which involved the caudal part of the NTS, the dorsal motor nucleus of the vagus (dmX), and portions of the hypoglossal nucleus, nucleus intercalatus and/or nucleus gracilis were found to label ascending fibers that, besides going to numerous brain stem territories that included prominently the parabrachial area, could also be traced to serveral forebrain structures, namely, the bed nucleus of the stria terminalis (BST), the paraventricular (PA), dorsomedial (HDM) and arcuate (ARC) nuclei of the hypothalamus, the central nucleus of the amygdaloid complex (AC), the medial preoptic area (PM) and the periventricular nucleus of the thalamus (TPV). Smaller isotope injections almost completely confined to the NTS and dmX resulted in lighter labeling of a similar set of parabrachial and forebrain projections, whereas in another case, in which the deposit was almost exclusively limited to the nucleus gracilis, no label was seen in the aforementioned structures. In another series of experiments, aimed at further localizing the neurons of origin of the prosencephalic projections under consideration, small microelectrophoretic HRP injections confined almost totally to BST, PA, HDM, AC, PM or TPV, as well as both small and large injections involving ARC, resulted in labeled neurons situated in the dorsal medullary region, mainly in the medial portion of the NTS at the level of and caudal to the area postrema. Taken together, these observations indicate for the first time the existence of relatively direct conduction lines by which interoceptive information might be conveyed to limbic forebrain structures; some of the possible physiological correlates of these anatomical findings are discussed.

Afferent Pathways↗

PubMed1981

Single cell activity in ventral prefrontal cortex of behaving monkeys.

Single unit activity was recorded extracellularly from ventral prefrontal cortex (VPC) of monkeys during performance of two short-term memory tasks: spatial delayed response and delayed matching to sample. The tasks required perception, retention and recognition of visual cues differing in either color or spatial location. Two separate areas of VPC were explored: a lateral area in the lower prefrontal convexity and a medial area around the medial orbital sulcus. Two categories of unit activity were distinguished on the basis of frequency changes to the cue. One was characterized by non-specific discharge independent upon which cue was presented, the other by discriminative discharge related not only to visual qualities of the cue but to the animal's subsequent use of it. Nearly one-half of all units showed altered firing during the retention (delay) period as compared with intertrial control firing. Eighteen per cent displayed delay activity related to the quality of the preceding cue. The lateral and medial segments of VPC were not distinguished by differences of unit activity in cue or delay periods. Post-trial activity was related to presence or absence of reward. Type I cells showed firing changes following choice reinforcement as well as gratuitous reward; some showed changes in opposite direction following unreinforced choices. They may encode the availability of reward. Type II cells showed changes of activity after unreinforced trials and, in some cases, opposite changes after unexpected reward; they were not affected by the reward of normal correct-choice trials. These cells appear to react to deviations from expectancy of reward. Type III cells exhibited comparable firing changes following reinforced and unreinforced choices. They may encode termination of a trial sequence. Type I was more common in lateral than medial VPC, whereas the opposite was true for type II; type III did not clearly predominant in either area. Ablation studies have shown that the two areas of VPC differ in behavioral functions. This study of their cellular properties revealed topographic differences only during the post-trial period. It is therefore possible that the combination of cue and delay activity (related to exteroceptive input) with post-trial activity (related to interoceptive input) constitutes the neuronal basis for the two areas' differences in behavioral function.

Animals↗

PubMed1991

Stimulation of catecholaminergic neurons in the ventral medulla by various stressors monitored with in vivo electrochemistry.

Catecholaminergic metabolism in the A1 cell group of the ventrolateral medulla oblongata was followed after application of 3 interoceptive stressful stimuli by monitoring the extracellular concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) with an in vivo voltammetric approach. These stimuli provoked an increase of the DOPAC signal with different time course and amplitude. Histamine led to a maximal 200% increase that vanished within two hours. Insulin induced a long-lasting increase of up to 350% that could be reversed by glucose infusion. Electrical stimulation of the sciatic nerve triggered an immediate increase of up to 140% which stopped with the ending of the stimulation. The time-course of this activation is compatible with a possible involvement of catecholaminergic afferents from the A1 group projecting to the paraventricular nucleus in the stimulation of the hypothalamic neurosecretory cells elicited by the stressors.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

Alexithymia in panic disorder and social phobia.

Two recent studies have found that small samples of panic disorder patients appear to have elevated levels of alexithymia and raised the possibility that panic patients may constrict emotional experience. An alternate hypothesis is that there is conceptual and measurement overlap between alexithymia and cognitive aspects of panic disorder, and panic patients may in fact score high on only one dimension of alexithymia. One hundred panic disorder patients and 46 social phobics completed the revised 20-item Toronto Alexithymia Scale (TAS) and several anxiety-related measures. Thirty-four percent of panic patients and 28.3% of social phobics were classified as alexithymics, a nonsignificant difference. However, the alexithymia dimension related to difficulties in identifying and differentiating emotions and physical sensations was significantly elevated as compared with the alexithymia dimension related to external-oriented thinking. The former dimension was also significantly correlated with anxiety measures. The apparent finding that a sizeable proportion of panic patients are alexithymic may be an artifact of conceptual and psychometric overlap with cognitive aspects of panic disorder, specifically the interoceptive focus and sensitivity often associated with panic attacks.

Adult↗

PubMed1975

Evidence for a cortical locus for the stimulus effect of nicotine.

This study investigated the stimulus properties of nicotine in the rat with the objective of determining the time course of the nicotine-produced interoceptive cue and its relationship to specific brain levels of the drug. The behavioral task employed was shock-escape in a T-maze apparatus. After the injection of nicotine entrance into the nicotine-correct arm of the T-maze resulted in termination of a 0.6 mA shock. When saline was administered, entrance into the opposite arm was rewarded by termination of shock. A high level of discrimination between nicotine and saline was obtained and the degree of discrimination was observed to decrease as the length of time period between nicotine administration and the test of discrimination was increased. This decline in discrimination was closely correlated with the decline in brain levels of nicotine in the cortex suggesting that the stimulus effect of nicotine is directly related to the concentration of nicotine in the cortex.

Animals↗

PubMed1987

A role for receptors of N-methyl-D-aspartic acid in the discriminative stimulus properties of phencyclidine.

Ketamine and (+)-N-allylnormetazocine ((+)-NANM) were found to generalize in a rat operant drug discrimination paradigm to the interoceptive stimulus induced by phencyclidine (PCP). Intraperitoneal administration of the non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, MK-801, and intracerebroventricular injection of the competitive antagonist, 2-DL-amino-7-phosphonoheptanoic acid (2-APH), also resulted in a dose-dependent generalisation to the PCP discriminative stimulus. The results suggest that NMDA receptor antagonism may play an important role in the mediation of the discriminative stimulus properties of PCP. The low potency of MK-801 and 2-APH to displace [3H](+)-NANM binding in vitro argues against an involvement of the haloperidol-sensitive sigma recognition site in the behaviour.

Animals↗

PubMed1988

The interaction between zolpidem and beta-CMC: a clue to the identification of receptor sites involved in the sedative effect of zolpidem.

The interaction of beta-CMC, an amino beta-carboline recently described as a selective antagonist of the sedative effect of diazepam, with zolpidem, an imidazopyridine hypnotic, which like beta-CMC binds preferentially to the omega 1 (BZ-1) site of the GABA benzodiazepine chloride channel receptor complex, was investigated. In mice, beta-CMC antagonized the effect of zolpidem against isoniazid-induced convulsions without affecting its activity against convulsions induced by pentylenetetrazole or electroshock. beta-CMC also antagonized the decrease in locomotor activity and the impairment in muscle strength provoked by zolpidem. In rats trained to discriminate zolpidem, beta-CMC antagonized both the interoceptive stimulus and the decrease in the rate of lever pressing produced by zolpidem. This selective antagonism, inhibition of effects of zolpidem exerted by low doses (locomotor activity and isoniazid-induced convulsions) as well as effects produced by high doses (muscle strength) but not those provoked by intermediate doses (pentylenetetrazole and electroshock-induced convulsions), could not be explained by a receptor occupancy hypothesis. These results suggest that the anticonvulsant and sedative effects of zolpidem do not involve the same receptor subtype and that the hypnoselective properties of zolpidem may be linked to its selectivity for the omega 1 (BZ-1) site of the GABAA receptor.

Animals↗

PubMed1992

The effect of 5-HT3 receptor antagonists on the discriminative stimulus effects of amphetamine.

The discriminative stimulus induced in rats by amphetamine has previously been shown to be due to raised mesolimbic dopamine levels. As 5-HT3 receptor antagonists have been shown to inhibit hyperactivity resulting from raised mesolimbic dopamine levels, the present study examined their effects against the amphetamine discriminative stimulus. None of the 5-HT3 receptor antagonists tested (MDL 72,222EF, 0.3-10 mg/kg s.c.; MDL 73,147EF, 0.3-10 mg/kg s.c.; ICS 205-930, 0.01-10.0 mg/kg s.c.; ondansetron, 0.1-1000 micrograms/kg s.c.) antagonised the effects of amphetamine in this test. This suggests that 5-HT3 receptors cannot modulate the effects of raised mesolimbic dopamine in pathways involved in the interoceptive effects of amphetamine.

Amphetamine↗

PubMed1993

Comparison of the behavioral effects of ibogaine from three sources: mediation of discriminative activity.

Ibogaine is an alkaloid employed for its hallucinatory properties in West Central Africa which has been the subject of alleged efficacy as an aid in the interruption and treatment of chemical dependency. The major sources of the Schedule I agent are: Sigma Chemical Co., the National Institute on Drug Abuse and as NDA International Inc.'s Endabuse. The intent of the present study was to, for the first time, train rats to discriminate the interoceptive stimuli produced by (10 mg/kg, intraperitoneally administered) ibogaine. Once trained, these rats were used to investigate the dose-response effects to ibogaine from each of the three suppliers. In addition, stimulus generalization to the dopamine antagonist CGS 10476B, as well as to the serotonergically active compounds fenfluramine, TFMPP (1-(m-trifluoromethylphenyl)piperazine, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane), MDMA (3,4-methylenedioxymethamphetamine), quipazine and LSD, was tested. The results indicate that ibogaine is readily discriminable from its vehicle and that ibogaine from each of the three supplies produced statistically similar discrimination with ED50 values ranging from 2.5 to 3.4 mg/kg. In addition, various doses of the novel drugs tested produced, at best, intermediate ibogaine-appropriate responding and, thus, no drug tested can be considered to generalize to ibogaine-like stimuli. Discussion concerns the multiple actions of ibogaine that have been cited in the scientific literature. The similarity in potency of ibogaine from three potential suppliers should allow for pre-clinical work using any of these research samples to be comparable.

Animals↗

PubMed1996

Time course of discriminative stimulus effects of bretazenil and chlordiazepoxide in rats.

The time course of the discriminative stimulus effects of a benzodiazepine partial agonist, bretazenil, and a benzodiazepine full agonist, chlordiazepoxide, were determined in rats after administration of two doses of either drug. As in man, bretazenil was considerably shorter-acting than chlordiazepoxide, with 0% drug-appropriate responding at the 2-h time point after the training dose of 7 mg/kg and < 20% drug-appropriate responding at 9 h after the 14 mg/kg dose. With chlordiazepoxide, responding on the water-appropriate lever did not occur in all rats until 7 h after administration of the training dose of 7 mg/kg, compared to 17 h after administration of 14 mg/kg. Although there was considerable individual variability with both drugs, it would appear that the drug discrimination procedure can be a valuable tool for studying the time course of the interoceptive effects of psychoactive drugs.

Animals↗

PubMed1985

Symbolic functioning in anorexia nervosa.

This study examined 20 patients with anorexia nervosa using a projective test with a quantitative scoring system (the SAT9), and an indirect measure of symbolic function (the interoceptive awareness subscale of the EDI). The findings support the clinical observation that patients with anorexia nervosa are often arrested developmentally, and are without the ability to deal adequately with the anxieties created by the process of maturation. The results of this study have significance for the psychotherapy techniques used in the treatment of these patients.

Adult↗