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PubMed1987

The interoceptive discriminative stimuli induced by the novel putative anxiolytic TVX Q 7821: behavioral evidence for the specific involvement of serotonin 5-HT1A receptors.

TVX Q 7821 is active in several behavioral models of anxiety in animals and has a high selective affinity for brain serotonin 5-HT1A receptors in binding assays. In order to determine if interaction with 5-HT1A receptors is important for some of the behavioral effects of this compound, 11 rats were trained to reliably discriminate the interoceptive stimuli induced by TVX Q 7821 (10 mg/kg, IP) from those of saline. Following discrimination acquisition, TVX Q 7821 administration resulted in drug-appropriate responding with an ED50 of 1.5 mg/kg, as did other substances with high affinity for the 5-HT1A receptor: 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, ED50 = 0.16 mg/kg), 5-methoxy-N,N-dimethyltryptamine (5-OMe-DMT, ED50 = 2.5 mg/kg), and buspirone (ED50 = 5.4 mg/kg). Anxiolytics not acting via the 5-HT1A receptor, like diazepam and pentobarbital, did not induce full TVX Q 7821-appropriate responses. In addition, non-selective 5-HT agonists and antagonists such as bufotenin, quipazine, and methysergide, as well as substances with high affinity for the 5-HT1B receptor (m-trifluoromethylphenylpiperazine, TFMPP; 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole succinate, RU 24969) did not substitute for TVX Q 7821. These data support a selective 5-HT1A mechanism of action in vivo for TVX Q 7821 and indicate the suitability of TVX Q 7821 for the investigation of behavioral correlates of the 5-HT1A receptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1996

Loss of tolerance to morphine after a change in route of administration: control of within-session tolerance by interoceptive conditioned stimuli.

Tolerance to morphine analgesia (tail-immersion test) was examined after manipulation of two aspects of a tolerance test: 1) the route of drug administration and 2) the time interval between the test dosing and the tolerance test. The intravenous (IV) and intraperitoneal (IP) routes were used, together with a novel test for tolerance in which the test morphine was infused IV just 2 min before measuring the opiate effect. The first experiment validated this test as an assay for tolerance by examining the log dose-response (LDR) curve changes produced by daily IP injection with 0, 20 or 200 mg/kg morphine; the IV test confirmed the expected parallel shift to the right and flattening of the LDR curve. In the second experiment, all rats of two groups were injected once daily for 3 weeks with 20 mg/kg morphine and with saline except that one group received the morphine IV (and saline IP), the other morphine IP (saline IV). The results indicated route-specific tolerance. On a test using 20 mg/kg given IV morphine, tolerance was significantly greater in rats treated with IV morphine than in those treated IP. However, a larger effect on tolerance was produced by a pretest application of 5 mg/kg morphine 30 min before the actual tolerance test. This manipulation was designed to "prime" short-term, adaptive processes hypothesized to occur within a normal tolerance test session as morphine is taking effect. The tolerance on the test increased (equivalent to 2 to 3 fold shift in the LDR curve) when the pretest morphine was given with the same route as the chronic morphine, regardless of treatment group. It was concluded that opiate tolerance may be modulated by conditioned stimuli produced by morphine acting through different routes. These interoceptive cues appear to modulate rapidly acquired and short-lived adaptive processes taking place within a given test session.

Analgesics, Opioid↗

PubMedDate not supplied

Effect of unconscious interoceptive afferentation on the spatial organization of electrical activity in the human cerebral cortex.

Toposcopic studies consisting of EEG recording from 24 cortical points was carried out to characterize the spatial organization of the electrical activity of the human cerebral cortex during the action of unconscious interoceptive stimuli arising from biologically active points associated with different internal organs-the heart, lungs, liver, and intestine. When acupuncture had positive effects, reductions in global synchronization of cortical potentials were noted, which were combined with foci of weakening of the linear and nonlinear correlations in the anterior parts of the right hemisphere, as well as in the posterior and temporal parts of the left hemisphere, with increases in coherence in one of the high-frequency subranges of the EEG (21.5-23.0 Hz). Negative effects and absence of effect correlated with significantly less pronounced weakening of global synchronization of potentials, and increases in their coherence in one of the subranges of alpha activity.

Acupuncture Points↗

PubMedDate not supplied

Interoceptive conditioning through repeated suppression of morphine-abstinence. II. Relapse-testing.

The reinforcing properties of etonitazene, both conditioned and unconditioned, were measured in rats that had received saline only by continuous intravenous infusion ("saline" group) and in two groups of rats that had been physically dependent on morphine to equal degrees (and presumably had developed equal degrees of tolerance to morphine): one by once daily passive intravenous injection of morphine ("injection" group) and the other by passive continuous intravenous morphine infusion at the same daily doses for approximately the same number of days ("infusion" group). Prior to passive saline and morphine administration, all rats were trained to press right- and left-sided levers for water reinforcement from 1600 to 0800 hrs to a not more than 60-40 split, and these and other measures ("baselines") were repeated after recovery from the early (acute) morphine-abstinence syndromes. Then etonitazene, 5 micrograms/ml, was substituted for water on the nonpreferred side and all measures were repeated from 1600 to 0800 hrs once every two weeks for 20 weeks (10 "relapse" tests). It was postulated that the daily cycles of morphine-abstinence and suppression of abstinence in the injection group only would generate latent interoceptively conditioned reinforcing properties of morphine because of conditioning of suppression of abstinence to the concomitant internal sensorial effects of morphine, which would persist after morphine withdrawal and be transferred to the internal effects of another opioid, etonitazene. It was found that across the first nine relapse tests, the injection group consumed significantly more etonitazene than the infusion group, while there were no significant differences in water consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Animal phobias versus claustrophobias: exteroceptive versus interoceptive cues.

The overall purpose of this investigation was to examine heterogeneity among specific phobias. In particular, the goals were to compare features of fear responding between individuals fearful of claustrophobic situations and individuals fearful of spiders/snakes, and to compare their response to hyperventilation challenges. By so doing, specific predictions were tested in relation to a conceptual model of exteroceptive and interoceptive fear cues. Using a nonclinical sample, 19 subjects with spider/snake phobias, 18 nonphobics, and 9 subjects with claustrophobias were exposed on two separate occasions to a live tarantula or python, a small closet, and a hyperventilation challenge. Dependent measures included subjective anxiety, panic attacks, physical symptoms, cognitive symptoms (or, fear of symptoms) and heart rate. In addition, subjects completed a standardized self-report scale that measures fear of bodily symptoms of arousal. It was found that subjects with claustrophobia reported more physical symptoms and cognitive symptoms than did subjects with snake/spider phobias, in response to their fear-relevant stimulus. In addition, claustrophobic subjects were more fearful of hyperventilation challenges and reported more fear of bodily symptoms, than did snake/spider phobic subjects. Finally, subjects with claustrophobia were as fearful of hyperventilation as they were of their fear-relevant stimulus. Theoretical and empirical implications of these findings are discussed.

Adult↗

PubMed1995

Awareness of blood pressure: interoception or contextual judgement?

Most patients with mild to moderate hypertension are asymptomatic but some patients report symptoms and seem to be aware of their blood pressure. The research question is whether the estimation of blood pressure is primarily derived from interoception or is inferred by contextual judgement. A psychophysiological ambulatory assessment was conducted with 51 male hypertensive patients and 30 either normotensive or hypotensive student subjects employing (1) a multichannel recording system for blood pressure, heart rate and physical activity; and (2) a pocket computer for assessing estimated BP, setting variables and self-ratings of subjective state. Within-subject correlations revealed that there was no significant relationship between estimated BP and concurrently recorded systolic BP. Estimated BP is, however, related to self-ratings of feeling physically tense and self-ratings of physical activity. Blood pressure awareness appears to be a rather inconsistent and subjective phenomenon, based on contextual judgements and inferences instead of "perception", but it is a relevant methodological issue (and possible bias) in hypertension research.

Adult↗

PubMed1979

The involvement of interoceptive factors in the maintenance of heroin-seeking behavior.

The role of interoceptive stimuli in conditioned heroin-seeking behavior was investigated using forty-two naive male Wistar rats. A 21-day Phase I period in which 28 animals self-injected heroin in saline solution was followed by a 5-day Phase II period in which 7 animals were allowed access to the original solution; 7 animals were allowed access to saline only; 7 animals were allowed access to distilled water; and 7 animals were allowed no access to any solution. Results showed that only the heroin and (heroin-associated) saline groups shows a significant difference in operant rate compared to animals that had been continually exposed to saline only. It was concluded that heroin-seeking behavior was maintained in the (heroin-associated) saline group as a result of physiological conditioning following repeated association of saline with heroin.

Animals↗

PubMed1988

The role of dopamine and serotonin receptors in the mediation of the ethanol interoceptive cue.

The drug discrimination paradigm was used to evaluate the contribution of dopamine or serotonin receptors in the mediation of the stimulus properties of ethanol. Briefly, rats were trained to discriminate between ethanol (600 mg/kg, IP) and water vehicle. Dose-response relationships were observed for ethanol and rats were tested with various dopamine and serotonin receptor agonists and antagonists. The specific dopamine receptor agonists SKF 38393 (DA1) and LY 171555 (DA2) failed to produce appreciable ethanol-like stimulus effects. Furthermore, the dopamine receptor antagonists SCH 23390 (DA1) and haloperidol (DA2) did not affect ethanol-appropriate responding when administered in combination with the training dose of ethanol. A number of specific serotonergic receptor ligands were also tested. Quipazine, 5-MeODMT, buspirone, 8-OH-DPAT elicited intermediate ethanol-like stimulus properties in rats. The serotonin receptor blockers pizotifen, pirenperone and (-)propranolol were ineffective in blocking the interoceptive cue produced by 600 mg/kg ethanol. However, TFMPP produced strong ethanol-like discriminative properties and completely substituted for the training dose of ethanol. These results indicate that the stimulus properties of TFMPP are similar to those of a low dose of ethanol.

Animals↗

PubMed1991

Increased generalization between drug-related interoceptive stimuli with delayed testing.

Although the flattening of generalization gradients over time has been widely investigated using exteroceptive stimuli, little attention has been given to generalization involving interoceptive stimuli. To investigate generalization between internal states, Sprague-Dawley rats were given either 0.835 ml/kg chloropent or 15 mg/kg sodium pentobarbital. Both drugs produced asymmetrical state-dependent retention of a passive avoidance response, that is, good retention in the "same state" conditions (i.e., the drug-drug and no drug-no drug conditions) as well as in the no drug-drug conditions but poor retention in the drug-no drug conditions, at both 1- and 7-day retention intervals. Furthermore, subjects trained in one drug state (pentobarbital or chloropent) demonstrated disrupted performance when tested 1 day later in another drug state, but good performance when tested 7 days later in the other drug state, indicating a decrement in the discriminability of the two drug states after 7 days. This outcome demonstrates that generalization gradients between drug states flatten over time. Moreover, these results suggest that memory for attributes of internal stimuli undergoes changes similar to those found for exteroceptive stimuli. Implications for contextual cues models of forgetting are considered.

Anesthetics↗

PubMedDate not supplied

Peripheral injections of vasopressin control behavior by way of interoceptive signals for hypertension.

The stimulus properties of peripheral injections of vasopressin were assessed using conditioned taste aversion techniques. Conditioned taste aversion induced by vasopressin was blocked by prior exposure to vasopressin but not to another aversive agent, apomorphine. Prior exposure to behaviorally equivalent doses of another hypertensive agent, angiotensin II, blocked also conditioned taste aversion induced by vasopressin and this effect was fully reciprocal, since prior exposure to AVP blocked the aversive effect of angiotensin II. The protection offered by prior exposure to angiotensin II was not due to an endogenous release of AVP since the aversive properties of angiotensin II were not blocked by administration of a specific antagonist of the vasopressor effects of vasopressin. These data suggest that the interoceptive cues which are responsible for the conditioned taste aversion induced by vasopressin are related to the hypertensive action of this peptide.

Angiotensin II↗

PubMed1989

The pentylenetetrazol-like interoceptive stimulus produced by ethanol withdrawal is potentiated by bicuculline and picrotoxinin.

We investigated whether the interoceptive discriminative stimulus (IDS) arising from ethanol withdrawal was related to decreased activity of the gamma-aminobutyric acid (GABA) system by determining whether the sensitivity of rats to the GABA antagonists was altered by chronic treatment with ethanol. Rats were trained to obtain food reward by responding on one lever following pentylenetetrazol (PTZ) and the other lever following saline. Whereas all of the trained rats selected the PTZ-appropriate lever after PTZ, no more than 50% of them selected this lever following an optimum dose of bicuculline or picrotoxinin. After either saline or diazepam (5 mg/kg), all of the rats selected the saline-appropriate lever. Ethanol (0.24 mol/kg/day) was then administered to the rats for 4 days via a nutritionally balanced liquid diet. Between 48 and 96 hours postethanol, 30% of the rats selected the PTZ-appropriate lever following saline, whereas selection of this lever was increased to 80% following either bicuculline or picrotoxinin. Thus, further antagonism of GABAergic activity increased the subjective effect of ethanol withdrawal. These data support the hypothesis that the PTZ-like IDS produced during withdrawal from ethanol is related to an ethanol-induced deficit in the activity of the GABA-benzodiazepine receptor-coupled chloride channel.

Animals↗

PubMed2004

Environmental modulation of the interoceptive effects of amphetamine in the rat.

The aim of the present study was to investigate the effect of environmental novelty on amphetamine discrimination. Two groups of rats (home group and novelty group) were trained to perform water-reinforced operant behavior in cages equipped with two levers and a retractable liquid dipper (0.1cc cup). The experimental procedures for the two groups were identical except for the fact that home rats were housed and tested in the operant cages whereas novelty rats were transferred daily to these cages for the testing sessions (25min). The rats were trained to discriminate one of two doses of amphetamine (0.25 and 0.5mg/kg) from saline. Saline and amphetamine were administered intraperitoneally immediately before each daily session according to a semi-random schedule for a total of 50 sessions. Reinforcements were delivered according to a fixed ratio that was increased daily from 2 to 30. Successful drug discrimination was achieved when activity on the appropriate lever before the first reinforcement was greater than 80% of total activity, on at least seven out of eight consecutive sessions. When training was conducted with 0.25mg/kg of amphetamine, no home rat acquired drug discrimination whereas 56% of novelty rats reached criterion. When training was conducted with 0.5mg/kg of amphetamine, drug discrimination was achieved by 50% of home rat versus 86% of novelty rats. These findings indicate that environmental novelty can alter the ability of amphetamine to produce interoceptive cues.

Amphetamines↗

PubMed2004

Contribution of tactile and interoceptive cues to the perception of the direction of gravity.

Without relevant visual cues, the Subjective Visual Vertical (SVV) is biased in roll tilted subjects toward the body axis (Aubert or A-effect). This effect is generally ascribed to changes in the vestibular and somatosensory inputs following a body tilt. This study focused on the contribution of interoception and tactile cues in the SVV. The body-cast technology and gastric fullness were used to obtain a diffuse tactile stimulation and an overload stomach stimulation, respectively. Fifteen subjects placed in a tilt-chair were rolled sideways from 0 degrees to 90 degrees. They were asked to adjust a luminous line to the vertical under two body restriction conditions (strapped vs. body-cast) and two stomach load conditions (empty vs. full). Results showed (1) an improvement in the SVV judgment when somaesthetic cues were available in the full stomach condition (p < 0.001), (2) an increased A-effect for the higher body tilt values in the body-cast condition (beyond 45 degrees, p < 0.001), and (3) a smaller disrupting effect of the body-cast in the SVV judgment in the full stomach condition (p < 0.05). Since the vestibular system produced the same gravity response in all conditions, it can be stated that somaesthetic cues are involved in the SVV. Tactile mechanoreceptors may have contributed by detecting the changing pattern of pressures generated on the skin that results from changes in body orientation. The stomach load may act through the inertial forces exerted against the gravity load when the stomach is full by the mechanoreceptors in the fundus. Thus, the somaesthetic system can indicate the direction of gravity via patterns of pressure within and at the surface of the body.

Adult↗

PubMed2005

On the relationship between interoceptive awareness, emotional experience, and brain processes.

The perception of visceral signals plays a crucial role in many theories of emotions. The present study was designed to investigate the relationship between interoceptive awareness and emotion-related brain activity. 44 participants (16 male, 28 female) first underwent a heartbeat perception task and then were categorised either as good (n = 22) or poor heartbeat perceivers (n = 22). A total of 60 different pictures (pleasant, unpleasant, neutral) from the International Affective Picture System served as emotional stimuli. EEG (61 electrodes) and EOG were recorded during slide presentation. After each slide, the subjects had to rate emotional valence and arousal on a 9-point self-report scale. Good heartbeat perceivers scored the emotional slides significantly more arousing than poor heartbeat perceivers; no differences were found in the emotional valence ratings. The visually evoked potentials of good and poor heartbeat perceivers showed significant differences in the P300 and in the slow-wave latency ranges. Statistical analyses revealed significantly higher P300 mean amplitudes for good heartbeat perceivers (averaged across all 60 slides) than for poor heartbeat perceivers. In the slow-wave range, this effect was found for affective slides only. Heartbeat perception scores correlated significantly and positively with both the mean arousal rating as well as with the mean amplitudes in the P300 time window and the slow-wave window. Our results demonstrate a strong relationship between the perception of cardiac signals and the cortical processing of emotional stimuli, as would be postulated for example by the James-Lange theory of emotions.

Adolescent↗

PubMed2005

Withdrawal, tolerance, and sensitization to dopamine mediated interoceptive cues in rats trained on a three-lever drug-discrimination task.

In the present experiment rats were trained on a three-lever, drug-discrimination task to discriminate the cues associated with 0.30 mg/kg of the indirect dopamine (DA) agonist, amphetamine (AMPH), saline (SAL), and 0.03 mg/kg of the DA, D2 receptor antagonist, haloperidol (HAL). Choice behavior determined from tests on 0.30 and 0.15 mg/kg AMPH, SAL 0.03 and 0.015 mg/kg HAL provided a behavioral baseline presumed to represent changes along a continuum of DA mediated, interoceptive cues. Results from separate groups tested on 0.30 and 0.15 mg/kg AMPH, SAL, 0.03 and 0.015 mg/kg HAL, 24 h post-treatment with an acute 7.5 mg/kg dose of AMPH, showed rapid tolerance and withdrawal to the AMPH cue and sensitization to the HAL cue. The same tests 24 h following treatment with 1.0 mg/kg HAL showed rapid tolerance to the HAL cue, sensitization to the AMPH cue, but not AMPH-like withdrawal cues. Analysis of the results showed that tolerance to the AMPH and HAL cues reflected neuroadaptive baseline shifts and not weaker cue properties. These findings are consistent with predictions from opponent process theory of motivation and provide an animal model to study the motivational consequences that aversive symptoms of AMPH withdrawal such as dysphoria and anhedonia can have on drug-taking behavior.

Amphetamine↗

PubMed2006

Regional cerebral blood flow changes associated with interoceptive awareness in the recovery process of anorexia nervosa.

BACKGROUND: An abnormality in regional cerebral blood flow (rCBF) in anorexia nervosa (AN) patients has been reported. There are very few studies that have investigated the rCBF changes in the recovery process of AN. METHODS: For eight female AN patients, we performed (123)I-IMP single photon emission computed tomography (SPECT) and four psychological assessments (Eating Disorder Inventory (EDI), Eating Attitude Test (EAT), Self-Rating Depression Scale (SDS) and State-Trait Anxiety Inventory (STAI)) both before and after inpatient-behavioral therapy. SPECT images were analyzed using statistical parametric mapping software. We also performed correlational analysis between rCBF and clinical variables. RESULTS: Following treatment, the patients showed significant body weight recovery. They showed significant improvement in EAT, SDS, STAI and a subscale of EDI - interoceptive awareness (IA) - but not in total EDI or other EDI subscales. Significant rCBF increases were observed in the precuneus, posterior cingulate cortex (PCC), right dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC) by the treatment. Significant correlation was observed between rCBF of right DLPFC and IA score before treatment. CONCLUSIONS: Changes of rCBF in right DLPFC, ACC, MPFC, PCC and precuneus were related to the AN recovery process and might be associated with improvement of IA following treatment.

Adolescent↗

PubMed2002

Cognitive therapy versus interoceptive exposure as treatment of panic disorder without agoraphobia.

Cognitive therapy (CT) and interoceptive exposure (IE) as treatments of panic disorder without agoraphobia were compared in a sample of 69 patients, randomly allocated to condition. There were no significant differences between treatments as to reductions in panic frequency, daily anxiety levels and a composite questionnaire score, at posttest after the 12-session treatment, and at both follow-ups (4 weeks, 6 months). In both conditions, high percentages of patients were panic free at post and follow-up tests (range 75-92%). Although the reduction in idiosyncratic beliefs about the catastrophic nature of bodily sensations was equally strong in both conditions, post-treatment beliefs correlated strongly with symptoms at post and follow-up tests in the CT condition, but not in the IE condition. Reduction of beliefs may be essential in CT, but not in IE. This suggests that the two treatments utilize different change mechanisms.

Adult↗

PubMed1997

Repeated exposure to interoceptive cues: does habituation of fear occur in panic disorder patients? A preliminary report.

In order to explore the mechanism of action of interoceptive exposure, 12 Panic Disorder (PD) patients were presented with two sessions of repeated CO2 inhalation. Two distinct patterns of responding were noted. The first pattern was described as habituation of fear (n = 6). These patients showed decrements in pre- and post-inhalation anxiety during both sessions (with more rapid decline during session 2), as well as spontaneous recovery of fear at the onset of session 2. The second pattern indicated fear sensitization. These patients showed relatively low levels of anticipatory anxiety preceding CO2 inhalation during both sessions but reported robust increases in fear following gas inhalation. The extent of this increase was slightly less during session 2 relative to session I and did not appear to be mediated by cardiovascular arousal, as both groups showed rapid HR habituation during both sessions. Results are discussed in light of current theories of PD and its treatment.

Administration, Inhalation↗