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PubMed2003

Eating behaviors and attitudes in women with infertility: a controlled study.

OBJECTIVE: Infertility arises from a complex pathogenic process in which it is often difficult to identify etiology. Psychological and behavioral factors may play a role in some cases of infertility. The extent to which eating behaviors and attitudes contribute to infertility is unknown. METHOD: In this study, 120 subjects with infertility, 80 fertile women, and 90 patients suffering from anorexia nervosa, restricting subtype (AN-R), were assessed with the Eating Disorder Inventory (EDI-2). RESULTS: The EDI-2 highlights differences among patients with AN-R and fertile and infertile subjects. Infertile patients had higher scores on the Interpersonal Distrust, Interoceptive Awareness, and Maturity Fears EDI-2 subscales than fertile subjects. Logistic regression identifies the independent variables of interpersonal distrust, interoceptive awareness, maturity fears, and asceticism as predictors of infertility. DISCUSSION: Infertile patients without eating disorders share some psychological features of women with AN. These features do not include disturbed eating attitudes and behaviors, but rather feelings of inadequacy, insecurity, and maturity fears.

Adolescent↗

PubMed2002

Volitional control of autonomic arousal: a functional magnetic resonance study.

Electrodermal activity reflects autonomic sympathetic innervation of dermal sweat glands providing an index of emotion-related bodily states of arousal. Relaxation techniques, which are facilitated by external (bio)feedback of electrodermal activity, can be used by trained subjects to actively control bodily and emotional arousal. Biofeedback relaxation provides an experimental model to explore neural mechanisms contributing to emotional representations and intentional autonomic control. We used functional magnetic resonance imaging (fMRI) to explore neural mechanisms contributing to integration of volitional intent, self-representation, and autonomic states of arousal, embodied within performance of a biofeedback relaxation exercise. Data were obtained from 17 subjects to assess brain activity during relaxation in which a visual index of electrodermal arousal was modulated by accuracy (addition of random "noise") or sensitivity (by scalar adjustments of feedback). A central matrix of cortical, subcortical and brainstem autonomic centres was activated during biofeedback relaxation, as well as regions that mediate visual and somatesthetic representations and executive control. Anterior cingulate, amygdala, and insula activity was modulated by task manipulations that increased demand on processing interoceptive representations, while variation in anterior insula activity reflected an interaction between accuracy and sensitivity of feedback. These findings identify neural substrates that support integration of perceptual processing, interoception, and intentional modulation of bodily states of arousal.

Adult↗

PubMed1988

Behavioral and physiological detection of classically-conditioned blood pressure reduction.

Spontaneously hypertensive (SH) rats were trained to discriminate the effects of saline injection from the interoceptive stimuli associated with the blood-pressure-reducing effect of clonidine (0.02 mg/kg, IP) in a drug discrimination procedure. Anise/ethanol and ethanol odors were then systematically paired with clonidine and saline treatment, respectively, outside the drug discrimination setting. As the number of pairings increased, the anise/ethanol (but not the ethanol) stimulus, when given alone, came to both reduce blood pressure and to mimic clonidine's interoceptive stimulus to virtually the same extent as clonidine itself. Both responses induced by the conditioned stimulus (CS+; anise/ethanol odor) were antagonized by the noradrenergic alpha-2 receptor antagonist yohimbine at a dose that did not by itself influence blood pressure. These data support the hypothesis that activation of endogenous factors can be elicited by a CS, and that these factors may furthermore act agonistically at central alpha-2 receptors to reduce blood pressure in hypertensive animals.

Animals↗

PubMed1983

Discrimination of systolic blood pressure.

The ability of humans to discriminate systolic blood pressure (BP) was investigated in two experiments. In Experiment 1, 14 normal subjects were asked to make estimates of their systolic BP while performing both BP-elevating and BP-lowering tasks. They were given intermittent feedback throughout all 10 45-min sessions. Results indicated significant correlations and small absolute differences between estimated and measured BP for all subjects in almost all sessions. Experiment 2, undertaken 6 months after Experiment 1, assessed whether estimation accuracy by subjects who had available both external and interoceptive cues surpassed that of subjects which access to external cues only. Three subjects from the original group who showed consistently high motivation, and who improved in accuracy across the 10 sessions in the previous experiment, made estimates of BP while performing novel tasks with no feedback. Correlations between estimated and measured BP remained high for 2 of the 3. These results were compared with the accuracy of control subjects (3 for each experimental subject) who were asked to estimate experimental subjects' BP using only the cognitive information available to the experimental subjects. Control subjects also had high correlations between their estimates and the experimental subjects' measured BP but at lower levels than two experimental subjects. These findings are discussed in relation to subjects' possible use of interoceptive information.

Adolescent↗

PubMed1994

Drug discrimination is a continuous rather than a quantal process following training on a VI-TO schedule of reinforcement.

Debate continues as to whether drug discrimination in animals is an inherently quantal or continuous process. This issue is important in determining the appropriate interpretation of results from drug discrimination studies designed to assess the nature of drug-induced interoceptive cues. The quantal approach holds that subjects perceive a drug cue in an all-or-none manner, while the continuous view proposes that when appropriate training and testing procedures are used, subjects can discriminate along a continuum of interoceptive cues. Data consistent with the quantal view have consistently been generated by animals trained to respond on schedules of reinforcement having an FR component. Since quantal responding is a characteristic of these schedules, results from drug discrimination studies using training schedules with FR components are of little value in empirically determining whether drug discrimination reflects a quantal or continuous process. Use of variable schedules of reinforcement might be more appropriate because the pattern of responding generated does not preclude results consistent with either of the competing views. Data from the following studies that trained subjects using VI schedules with a concurrent TO for incorrect lever responding were analyzed: Barrett et al. (1982): L-5-hydroxytryptophan versus saline; Smith (1990): diazepam versus pentylenetetrazol; Barrett et al. (1992): amphetamine versus haloperidol; Barrett and Steranka (1983): amphetamine versus haloperidol. In every case, when experimental conditions produced a group mean intermediate to that for the training drugs, the distribution of scores for individual animals was normally rather than bimodally distributed.

5-Hydroxytryptophan↗

PubMed1988

The chlordiazepoxide/pentylenetetrazol discrimination: characterization of drug interactions and homeostatic responses to drug challenges.

Rats were trained to discriminate chlordiazepoxide (CDP) from pentylenetetrazol (PTZ) in a two-lever food motivated discrimination task. Training drug doses were adjusted until subjects emitted approximately 50% of their responses on each of the two drug-appropriate levers during saline injection tests. Tests that followed injection of CDP/PTZ combinations illustrated a reciprocal antagonism between the two drugs. Saline-injection tests that followed large dose injections of CDP revealed a period of predominantly PTZ-appropriate responding that persisted after the initial period of predominantly CDP-appropriate responding. These data are interpreted to suggest that, unlike some other drugs that have been shown to antagonize the behavioral and CNS effects of benzodiazepines, the interoceptive stimulus generated by PTZ occupies a position opposite to that of CDP along some single affective continuum. In addition, these data suggest that drug/drug (DD) discriminations are capable of characterizing the interactions between training drugs. Finally, the data suggest that the CDP/PTZ discrimination is a sensitive detector of bidirectional shifts in interoceptive stimulus state along the CDP/PTZ continuum.

Animals↗

PubMed2005

Stress plays a role in the association between cognitive constructs and measures of eating disorders in male subjects.

OBJECTIVE: Several theorists have hypothesized that stressful situations may trigger abnormal eating and even eating disorders in predisposed people. The purpose of this study was to assess whether a stressful situation would reveal an association between perfectionism and low self-esteem, and measures of eating disorder symptoms in male high school students. METHOD: A sample of 61 male high school students completed the Eating Disorder Inventory, the Multidimensional Perfectionism Scale, and the Self Liking and Competence Scale three times: on an average school day, on the day of an exam and on the day the subjects received the results of that exam. Linear regression analysis was carried out to verify whether the dimensions of perfectionism were associated with the measures of eating disorders. RESULTS: Interoceptive awareness was associated with 'Bulimia' only during the stressful situation and with 'Drive for thinness' both in stress and non stress situations. Other results were contradictory and difficult to interpret. DISCUSSION: The results suggest that in nonclinical male individuals stress might bring out a previously absent association between some psychological predisposing factors for eating disorders and an actual desire or plan for ED related thoughts and behaviours. Such a finding suggests that stress may stimulate behaviours related to eating disorders in a predisposed personality. A central role may be played by interoceptive awareness in male subjects.

Adolescent↗

PubMed2000

Self-functioning traits affecting meal compliance in eating disorder patients.

The objective of this study was to measure the extent to which self-functioning traits relate to meal compliance in eating disorder patients by using multiple regression analysis. Compliance was the dependent variable. It was recorded on a meal flowsheet during breakfast, lunch and dinner and compiled for the 8 days immediately preceding each patient's discharge. The independent variables were gender, self-esteem (Rosenberg Scale) and 7 subscales of the Eating Disorder Inventory (EDI-2): drive for thinness, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness and maturity fears. A random sample of 30 subjects who completed the above instruments before May 1999 were included in the study. The results suggest that close to 50% of their meal compliance can be explained by variations in four explanatory variables: gender, ineffectiveness, interoceptive awareness and distrust. The adjusted r2 was 0.497 and the significance of the equation, measured by the p-value, was p = 0.0002. We conclude that multiple regression analysis is a valuable tool to identify patients' traits with the strongest effect in meal compliance.

Adolescent↗

PubMed2003

Cocaine-induced locomotor activity and cocaine discrimination in dopamine D4 receptor mutant mice.

RATIONALE: Previous studies have found a role for dopamine D(2)-like receptors in many of the behavioral effects of cocaine, including its stimulation of locomotor activity and interoceptive discriminative-stimulus effects. However, given the lack of selectivity of most of the available pharmacological tools among D(2), D(3) and D(4) dopamine receptors, the roles of these specific receptors remain unclear. OBJECTIVES: The roles of specific dopamine D(4) receptors in the behavioral effects of cocaine, including its locomotor stimulant and interoceptive discriminative-stimulus effects were investigated using dopamine D(4) receptor knockout (DA D(4)R KO) and wild-type (WT) mice. METHODS: The mice were trained in daily sessions to discriminate IP injections of saline from cocaine (10 mg/kg). Responses on one of two response keys intermittently produced a food pellet; one response was reinforced in sessions following cocaine injection (10 mg/kg), and the other response was reinforced in sessions following saline injection. Each 20th response produced a food pellet (fixed-ratio, or FR20 schedule of reinforcement). The dose-effects of cocaine and its interaction with the D(2)-like antagonist, raclopride, were assessed. Horizontal locomotor activity was also assessed in each genotype. RESULTS: As previously shown), cocaine was a more potent stimulant of locomotor activity in the DA D(4)R KO mice compared to WT littermate mice. In addition, cocaine was more potent in producing discriminative-stimulus effects in DA D(4)R KO mice (ED(50) value=0.50 mg/kg) compared to their WT littermates (ED(50) value=2.6 mg/kg). Raclopride shifted the cocaine dose-effect curve in both DA D(4)R KO and WT mice, though the shift was greater for the DA D(4)R KO mice. CONCLUSIONS: The present results on the stimulation of activity and interoceptive/subjective effects of cocaine are consistent with the previously reported disregulation of dopamine synthesis in DA D(4)R KO mice, and further suggest a role of the DA D(4)R in vulnerability to stimulant abuse.

Animals↗

PubMed2006

Neuroimaging and pain: a window on the autonomic nervous system.

Pain is one of the most common experiences of humans. Neuroimaging techniques can visualize the main brain areas involved in pain modulation, the pain matrix. It is noteworthy that many of the brain areas forming the pain matrix are also involved in modulating autonomic nervous system (ANS) activity that in turn plays a major role in determining the best adaptive response to the pain experience. The tight connection between the pain system and ANS is also evident from neuroanatomical studies indicating that the lamina 1 neurons receive both painful and visceral stimuli from all visceral organs giving rise to the spinothalamocortical pathway concerned with conveying interoceptive information to central structures. The resulting interoceptive stream projects to the viscerosensory cortex in the mid-insula and onto the right anterior insula and orbitofrontal cortices. Right anterior insula activation is involved in the sympathetic arousal associated with mental tasks. This brain region receives numerous other inputs including pain and painful stimuli are conveyed somatotopically to both insulae. A similar somatotopic organization of painful stimuli has also been shown in the basal ganglia involved in cognitive, affective, motor and autonomic states. This highly specialized organization of nociceptive information in these brain areas may subserve a number of functions, particularly of coupling pain with the most appropriate autonomic states and affective/emotional states. The anterior cingulated cortex, another brain area playing a crucial role in nociception, is also directly involved in the control of autonomic functions such as arousal during volitional behaviour, including effortful cognitive processing. It is evident that the nociceptive system and ANS closely interact in many processes involved in maintaining internal homeostatis and in order to give the most appropriate biological substrate for cognitive, affective and emotional states.

Autonomic Nervous System↗

PubMed1992

The reduction of claustrophobia--I.

The purpose of this study was to investigate the process of change during three interventions for claustrophobia, with particular reference to cognitive changes. Forty-eight participants, recruited from the community through the local media, were randomly assigned to one of four groups: pure exposure, exposure to the sensations of anxiety (interoceptive exposure), modification of negative cognitions, or a control group. All interventions were given over three sessions. The exposure group proved superior to the control on a wide range of measures. In the cognitive group, scores of reported fear and panic, declined significantly. The interoceptive group made some modest gains. An analysis of the timing of fear reduction and of treatment generalization, provides some indications of the mechanism of change.

Adult↗

PubMed1991

Characterization of tiagabine (NO-328), a new potent and selective GABA uptake inhibitor.

Tiagabine (NO-328) (R(-)-N-[4,4-bis(3-methylthien-2-yl)but-3-enyl]nipecotic acid, hydrochloride) is a new centrally acting GABA uptake inhibitor. The anticonvulsant activity of tiagabine was evaluated against seizures induced by methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), pentylenetetrazol, bicuculline, maximal electrostimulation (MES), or high intensity sound. The sedative actions of tiagabine were evaluated in tests for traction, rotarod performance and exploratory behavior. Finally, interoceptive properties of tiagabine were assessed using diazepam-, CGS 9896-, pentylenetetrazol-, or amphetamine-discriminating rats. Tiagabine was an effective anticonvulsant in doses which did not produce sedation or motor debilitation, although it was not potent against MES. In a manner similar to other anti-epileptic drugs, tiagabine potentiated dopaminergic function (methylphenidate-induced gnawing in mice) although it did not substitute for amphetamine in amphetamine-trained animals. Furthermore, although tiagabine antagonized DMCM-induced convulsions, it exhibited neither CGS 9896 or diazepam-like interoceptive effects, nor did it block (or potentiate) pentylenetetrazol-discrimination. Thus, GABA uptake inhibition represents a novel rationale for a valproate-like anticonvulsant drug therapy.

Animals↗

PubMed1987

Modulation of the discriminative stimulus produced by pentylenetetrazol by centrally administered drugs.

Pentylenetetrazol is anxiogenic in humans and produces an interoceptive discriminative stimulus in rats which is mimicked by anxiogenic drugs and other treatments and antagonized by anxiolytic drugs. It was proposed that the discriminative stimulus of pentylenetetrazol originates centrally. This hypothesis was tested by injecting small amounts of anxiogenic or anxiolytic drugs into the brain and comparing their ability to mimic or block, respectively, the response to pentylenetetrazol, observed after systemic injection. Food-restricted rats were trained in a two-lever operant task to discriminate the interoceptive discriminative stimulus produced by pentylenetetrazol. Intraperitoneal or intracerebroventricular injection of Ro 5-3663 was substituted in a dose-dependent manner for the stimulus produced by systemically administered pentylenetetrazol. Diazepam injected systemically, blocked the pentylenetetrazol-like stimulus associated with Ro 5-3663 administered systemically or centrally. Midazolam injected intracerebroventricularly and in a dose-dependent manner, antagonized the discriminative stimulus produced by systemic injection of pentylenetetrazol. When injected into the amygdala, midazolam also antagonized in a dose-dependent manner the pentylenetetrazol-induced stimulus. Thus, these data suggest that there are sites in the CNS for both the initiation of a pentylenetetrazol-like stimulus by Ro 5-3663 and the antagonism of the stimulus produced by pentylenetetrazol by midazolam.

Amygdala↗

PubMed1987

Enhancement of a diazepam withdrawal symptom by bicuculline and yohimbine.

The role of the GABA system in producing a pentylenetetrazol-like interoceptive discriminative stimulus during withdrawal from diazepam was investigated in rats by determining the sensitivity of this system to GABAergic drugs before and after chronic treatment with diazepam. Food-restricted rats were trained to obtain a reward of food by responding on one lever following an injection of pentylenetetrazol (PTZ; 20 mg/kg) and the other lever following an injection of saline (1 ml/kg). After rats had acquired this discrimination, the effectiveness of Ro 15-1788, bicuculline and yohimbine to substitute for pentylenetetrazol was determined. Prior to chronic treatment with diazepam, rats selected the appropriate lever for saline after Ro 15-1788 and the appropriate lever for pentylenetetrazol after bicuculline (0.04-2.5 mg/kg) or yohimbine (0.16-5.0 mg/kg). Although the selection of the appropriate lever for pentylenetetrazol was dose-dependent, full substitution for pentylenetetrazol was not obtained with either drug as larger doses of bicuculline produced convulsions while the rats began to select the appropriate lever for saline after larger doses of yohimbine (bell-shaped curve). Diazepam blocked the pentylenetetrazol-like interoceptive discriminative stimulus for bicuculline. The rats were then injected with diazepam (80 mg/kg/8 hr) for 24 days. Upon termination of the administration of diazepam, the animals were tested for lever-selection following the administration of saline, Ro 15-1788 (10 mg/kg), bicuculline (0.32, 0.64 and 1.25 mg/kg) or yohimbine (0.16, 0.64 and 2.5 mg/kg). After saline, 33% of the rats selected the appropriate lever for pentylenetetrazol whereas selection of this lever was enhanced after Ro 15-1788, bicuculline or yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Discriminative stimulus properties of mescaline: mescaline or metabolite?

The purpose of this study was to investigate possible similarities in the interoceptive stimuli produced by mescaline and its metabolites. Rats were trained in a 2 lever operant chamber to discriminate between the drugged state (mescaline 25 mg/kg) and the nondrugged state (saline). Following acquisition of discriminative response control the rats were pretreated with either saline, aldehyde dehydrogenase inhibitors or amine oxidase inhibitors and tested stimulus generalization produced by i.p. injections of 3, 4, 5-trimethoxyphenylethanol (TMPE), 3, 4, 5-trimethoxyphenylacetaldehyde (TMPA), N-acetylmescaline, mescaline or saline. The results indicated that both aldehyde dehydrogenase and amine oxidase inhibitors enhanced the effects of mescaline, while TMPE, TMPA and N-acetylmescaline failed to exhibit generalization to the mescaline state, regardless of pretreatment. These findings do not indicate the role of a metabolite in the interoceptive cue produced by mescaline.

Aldehyde Oxidoreductases↗

PubMed1994

Perceptual masking of the chlordiazepoxide discriminative cue by both caffeine and buspirone.

Twelve male Sprague-Dawley rats were trained to discriminate between the interoceptive stimulus attributes of 5 mg/kg chlordiazepoxide (CDP) and saline in a two-lever operant task under a fixed-ratio 10 (FR-10) schedule of food reinforcement. Caffeine, buspirone, and Ro 15-1788 failed to engender complete generalization when tested in combination with saline. In drug interaction test sessions caffeine (56 mg/kg) blocked the discriminative stimulus properties of the training dose of CDP and shifted the CDP discriminative dose-response function to the right. This rightward shift in CDP discriminative function was paralleled by a concomitant downward shift in the rate-of-responding dose-response function. Drug interaction test sessions conducted with 3.2 mg/kg of buspirone in combination with various doses of CDP engendered a downward shift in both the discriminative and rate-of-responding dose-response functions. Because 3.2 mg/kg buspirone in combination with the training dose of CDP resulted in complete response rate suppression, additional combination tests were conducted with 3 mg/kg CDP, a dose which reliably engendered > 90% CDP-appropriate responding, and various doses of buspirone. Similar to the CDP-caffeine interactions, buspirone blocked the cueing properties of 3 mg/kg CDP with a parallel reduction in response rates. Interaction test sessions conducted with Ro 15-1788 and CDP resulted in rightward shifts in both the discriminative and rate functions of CDP. We suggest that the interactions between CDP and both caffeine and buspirone resulted from the perceptual masking of the interoceptive (subjective) effects of CDP, whereas the interaction between Ro 15-1788 and CDP reflect pharmacological antagonism.

Animals↗

PubMedDate not supplied

Adrenocorticotropic hormone fragment ACTH/MSH(4-10 can act as a discriminative stimulus in rats.

Five of eight male albino rats learned to discriminate the effects of ACTH/MSH(4-10) (100 micrograms/kg, SC) from those of saline vehicle in a food-reinforced T-maze task. Generalization tests showed that the ACTH/MSH(4-10) cue was dose related with an ED50 of approximately 68.0 micrograms/kg. These findings indicate that ACTH/MSH(4-10) has interoceptive stimulus properties discriminable to some animals, which might provide a useful model for studying the pharmacology of this neuroactive peptide. Moreover, since ACTH/MSH(4-10) induces effects similar to those of ACTH/MSH in the central nervous system but not hormonally, these data suggest that endogenous ACTH or MSH may also have interoceptive stimulus effects unrelated to peripheral endocrine activity.

Adrenocorticotropic Hormone↗

PubMed1991

Effect of serotonin depletion by p-chlorophenylalanine upon discriminative behaviours.

1. Para-chlorophenylalanine (p-CPA), a competitive inhibitor of the serotonin (5-HT) synthesis enzyme tryptophan hydroxylase, was administered to rats at a dosage (100 mg/kg daily for 3 days) that depletes 5-HT. 2. Different groups of these rats were previously trained to discriminate the interoceptive stimuli produced by amphetamine, cathinone, 3,4-methylenedioxymethamphetamine (MDMA), N-ethyl-3,4-methylenedioxyamphetamine (MDE), fenfluramine or yohimbine, and the effect of p-CPA pretreatment upon their discriminative performance was compared with the effect of saline (control) pretreatment. 3. p-CPA was shown to have no effect upon the dopaminergically-mediated stimuli produced by the stimulants amphetamine and cathinone or upon yohimbine performance. 4. p-CPA significantly decreased discriminative performance with the serotonergic releasing drugs MDMA, MDE and fenfluramine. This decrease in discriminative performance returned to pre-p-CPA (criterion) levels at a time (9-12 days) when 5-HT has been reported to replete to normal brain concentrations. 5. It is concluded that p-CPA pretreatment lowers brain 5-HT and, in turn, significantly decreases the ability of rats to discriminate centrally active drugs whose interoceptive cueing stimuli are mediated by 5-HT neurons.

Animals↗