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PubMed1996

Effect of multiple discrimination reversals on acquisition of a drug discrimination task in rats.

There are many similarities between exteroceptive stimuli and interoceptive stimuli. Nevertheless, it has been suggested that behavior maintained by drug stimuli might be more difficult to reverse than behavior controlled by exteroceptive stimuli. Once a discrimination is established with an exteroceptive stimulus, it can be reversed by switching the reinforcement contingencies, and repeated reversals result in progressively faster relearning of the discrimination. To determine whether faster relearning of successive discrimination reversals also occurs when the discrimination is controlled by an internal drug stimulus, we trained rats to discriminate 3.2mg/kg phencyclidine-(PCP) from saline, in a two-lever food-reinforced operant task. After this discrimination was acquired, the reinforcement contingencies were reversed. A number of such discrimination reversals were performed to determine whether fewer trials would be needed to reach criterion performance with each reversal. Each time the reinforcement contingencies were switched, fewer training sessions were required for the subjects to reach criterion. These results are similar to those observed when a discrimination has been established with exteroceptive stimuli. The present study provides further evidence of the similarity between interoceptive drug stimuli and exteroceptive sensory stimuli.

Journal Article↗

PubMed2004

Differential neurosensitivity to the discriminative stimulus properties of ethanol in C57BL/6J and C3H/He mice.

BACKGROUND: A large body of evidence suggests that the interoceptive cue associated with ethanol intoxication is complex and dependent on a number of environmental and biological factors. Despite the fact that mice have been widely used to study genetic influences on sensitivity to various actions of ethanol, few studies have used mice to examine sensitivity to the discriminative stimulus effects of ethanol. The purpose of this study was to compare sensitivity to the discriminative stimulus effects of ethanol in two inbred mouse strains, namely C57BL/6J and C3H/He mice. METHODS: Adult male C57BL/6J and C3H/He mice were trained to discriminate between ethanol and saline using a two-lever food reinforcement operant procedure. Once criterion discrimination performance was achieved, dose-response functions were determined from generalization tests. Additional experiments were conducted to determine whether differences in discrimination performance were related to differential blood/brain ethanol levels in the two mouse strains. RESULTS: A greater proportion of C57BL/6J mice acquired the discrimination and required fewer trials to achieve criterion performance compared with C3H/He mice with a 1.0 g/kg ethanol training dose. This deficit in acquisition was overcome when the training dose was increased to 2.0 g/kg for C3H/He mice. In a second experiment, a 1.5 g/kg training dose of ethanol was used for both strains. Again, a greater proportion of C57BL/6J mice acquired the discrimination and required fewer training trials to achieve criterion performance compared with C3H/He mice. Blood ethanol levels did not differ between the strains after administration of the 1.5 g/kg training dose. However, blood and brain ethanol levels did differ between the strains after doses of ethanol were administered that produced equivalent discrimination performance. CONCLUSIONS: Results indicate that ethanol discrimination was more readily acquired and maintained in C57BL/6J mice than C3H/He mice. Ethanol dose-response functions generated from generalization tests also clearly demonstrated greater sensitivity to the discriminative stimulus properties of ethanol in C57BL/6J mice compared with the C3H/He strain. This differential sensitivity to the interoceptive cue produced by ethanol does not seem to be related to learning or pharmacokinetic differences between the two inbred strains.

Animals↗

PubMed2003

Discriminative stimulus properties of antidepressant agents: a review.

Though drug discrimination techniques have proven invaluable in characterizing the interoceptive properties of drugs of abuse, antipsychotics and anxiolytics, with the exception of some fragmentary data with tricyclic agents, surprisingly few studies have been undertaken with antidepressants. Nevertheless, the preferential dopamine (DA) reuptake inhibitor, bupropion, elicits a robust discriminative stimulus in rodents. Moreover, in rats trained on a two-lever FR-10 schedule for food reward, the selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram, and the noradrenaline (NA) reuptake inhibitor (NARI), reboxetine, elicit discriminative stimuli at doses that selectively elevate extracellular levels of 5-HT and NA, respectively. In generalization tests, mixed inhibitors of 5-HT and NA reuptake, such as venlafaxine, substitute for both citalopram and reboxetine, while SSRIs substitute for citalopram but not for reboxetine. Intriguingly, selective NARIs appear to substitute both for reboxetine and for citalopram though, owing to long-term instability of the citalopram cue, the latter observation will require confirmation. Bupropion and the atypical antidepressant, mirtazapine - a 5-HT2/alpha2-adrenoceptor (AR) antagonist devoid of affinity for 5-HT and NA reuptake sites - substitute for neither citalopram nor reboxetine, indicating that 'antidepressant' effects per se do not account for their interoceptive properties. Moreover, mirtazapine abolishes the citalopram cue, an action mimicked by the selective 5-HT2C antagonist, SB242,084. The discriminative stimulus elicited by reboxetine is blocked by the alpha1-AR antagonist, prazosin. In contrast, it is not significantly attenuated by the alpha2-AR antagonist, RX821,002, nor by betaxolol or ICI118,551, antagonists at alpha1- and alpha2-ARs, respectively. These observations indicate that 5-HT2C receptors and alpha1-ARs contribute to the discriminative stimulus properties of SSRIs and NARIs, respectively. The present article reviews the literature devoted to the discriminative stimulus properties of antidepressant agents as training drugs, focusing in particular upon novel data with citalopram and reboxetine. In addition, several open questions and future research directions are evoked. It would be of considerable interest to extend such drug discrimination studies to other classes of antidepressants or potential antidepressants, including venlafaxine, mirtazapine and antagonists at neuropeptide (corticotropin releasing factor1 and neurokinin1) receptors.

Animals↗

PubMed2003

Discrimination of a single dose of morphine followed by naltrexone: substitution of other agonists for morphine and other antagonists for naltrexone in a rat model of acute dependence.

Rats were trained to discriminate 4-h pretreatment with 10 mg/kg morphine and 15-min pretreatment with 0.3 mg/kg naltrexone (morphine-->naltrexone) from pretreatment with saline and 0.3 mg/kg naltrexone (saline-->naltrexone). The discrimination seems to derive from interoceptive stimuli from antagonist-precipitated withdrawal from acute morphine dependence. The purpose of this study was to extend pharmacological characterization of the discrimination by testing opioid agonists other than morphine and antagonists other than naltrexone. Of seven mu-opioid agonists tested in place of morphine, only two (heroin and levorphanol) substituted completely for it; trials completed on the morphine-->naltrexone-appropriate lever increased as a function of agonist and naltrexone dose. Agonists with intrinsic efficacy higher (etorphine, fentanyl, and methadone) or lower (buprenorphine and meperidine) than that of morphine substituted only partially. However, when naltrexone was administered during continuous infusion of fentanyl or methadone via s.c. osmotic pump, rats responded as if they had received morphine-->naltrexone; discriminative responding correlated with global withdrawal scores. Rats responded primarily on the saline-->naltrexone-appropriate lever when naltrexone was administered after pretreatment with dextrorphan, the dextrorotatory isomer of levorphanol, or kappa-opioid agonists (5-alpha,7-alpha,8-beta)-(+)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl]-benzeneacetamide (U69,593) and spiradoline. Antagonists with no intrinsic efficacy at mu-opioid receptors (naloxone and diprenorphine) substituted completely for naltrexone, whereas those with some efficacy (nalorphine and levallorphan) substituted partially. Thus, morphine-->naltrexone-like stimulus control of behavior by drugs administered acutely requires pretreatment with certain mu-opioid agonists and a pure antagonist, is independent of agonist efficacy, and is stereoselective. Interoceptive stimuli from naltrexone-precipitated opioid withdrawal are more similar across morphine-like agonists during chronic dependence than they are during acute dependence.

Acute Disease↗

PubMed1985

ACTH and corticosterone secretion in rats following removal of the neurointermediate lobe of the pituitary gland.

Surgical removal of the neurointermediate lobe of the pituitary gland (NIL-X) in the rat resulted in two abnormalities in ACTH secretion: (1) plasma ACTH and corticosterone levels were elevated in the morning and over a 24-hour period compared with levels in control (NIL-C) rats, and (2) although NIL-X and NIL-C rats had acute increases in plasma ACTH and corticosterone of equal magnitude after interoceptive stimuli (hemorrhage, surgery), NIL-X rats demonstrated markedly smaller elevations in plasma levels of these hormones after neurotropic stimuli (noise, novel environment). This subnormal adrenocortical response of NIL-X rats was not due to an impairment in perception of a neurotropic stimulus; these rats had normal latencies to paw licking and to jumping off a heated surface, yet smaller increases in plasma corticosterone after the stimulus. The impairment in ACTH response was not related to stimulus intensity, as NIL-X and NIL-C rats had equal ACTH and corticosterone secretion during both low and high levels of insulin-induced hypoglycemia. NIL-X rats demonstrated a significant elevation in daily water intake, although hematocrit, plasma Na+, K+, osmolality and protein were normal. Significant diurnal rhythms in plasma corticosterone levels and in water intake were maintained as well. The elevated morning plasma ACTH levels, the blunted hormone increases after noise, and the increase in water intake persisted in NIL-X rats 2 months after surgery. These data indicate that removal of the NIL results in (1) chronic elevations in basal ACTH and corticosterone secretion, and (2) chronic impairment in adrenocortical responses to neurotropic stimuli, but not to interoceptive stimuli. The deficit is not due to impaired perceptual capacity nor to the intensity of the stimulus.

Adrenocorticotropic Hormone↗

PubMed1996

Does exposure to internal cues enhance exposure to external cues in agoraphobia with panic? A pilot controlled study of self-exposure.

BACKGROUND: The value of internal (interoceptive) cues for exposure is under debate and so was tested in a pilot controlled study. METHODS: Outpatients with panic disorder and severe agoraphobia were randomised to 10 weeks of self-exposure to either (1) both internal (interoceptive) and external cues (n = 12) or (2) external cues only (n = 14). Both groups were trained in slow deep breathing and asked to carry out daily self-exposure homework. Neither group had cognitive restructuring. RESULTS: By post-treatment and follow-up all outcome measures improved significantly in both treatment groups. The two groups did not differ significantly in outcome, though slightly more patients who had exposure to both internal and external cues improved 50% or more on phobic avoidance and fear. CONCLUSIONS: A larger controlled study is now worthwhile to tell if such small differences can be significant.

Adolescent↗

PubMed2003

A twin study of genetic and environmental influences on psychological traits of eating disorders in a Japanese female sample.

The purpose of the present study was to clarify genetic and environmental origins of psychological traits of eating disorders using a Japanese female twin sample. Participants were 162 pairs of female twins consisting of 116 pairs of monozygotic (MZ) twins and 46 pairs of dizygotic (DZ) twins in their adolescence. Psychological traits of eating disorders were assessed with five subscales of the Eating Disorder Inventory (EDI). As a result of using univariate twin analyses, among five subscales of EDI (maturity fears, ineffectiveness, interpersonal distrust, interoceptive awareness, and perfectionism), perfectionism showed significant additive genetic contributions and individual specific environmental effects. On the other hand, maturity fears, ineffectiveness, interoceptive awareness, and interpersonal distrust indicated significant shared environment contributions and individual specific environment effects. The results suggest the importance of both genetic and shared environmental influences on psychological traits of eating disorders in the present study.

Adolescent↗

PubMed1984

Alcoholic denial: a biopsychological interpretation.

A theory of the origins and mechanisms of denial, which is frequently characteristic of alcoholics, is proposed on the basis of a biopsychological rather than a psychodynamic model of emotion. The biopsychological approach views denial as a consequence of a developmental defect in the apperception of interoceptive stimuli and in the appraisal of the significance of environmental events. Three hypotheses must be substantiated in order to support this theory: (1) alcoholics were physiologically unstable in arousal regulation; (2) alcoholics cannot cognitively discriminate interoceptive cues and physiological states; and (3) alcoholics cognitively underestimate emotion-laden events in their lives. Research which demonstrates the validity of these hypotheses is reviewed and implications for future research and treatment strategies are discussed.

Alcoholism↗

PubMed2004

The use of VR in the treatment of panic disorders and agoraphobia.

Panic disorder with agoraphobia (PDA) is considered an important public health problem. The efficacy of cognitive-behavioral therapy (CBT) for PDA has been widely demonstrated. The American National Institute of Health recommended Cognitive-Behavioral programs as the treatment of choice for this disorder. This institution also recommended that researchers develop treatments whose mode of delivery increases the availability of these programs. Virtual Reality based treatments can help to achieve this goal. VR has several advantages compared with conventional techniques. One of the essential components to treat these disorders is exposure. In VR the therapist can control the feared situations at will and with a high degree of safety for the patient, as it is easier to grade the feared situations. Another advantage is that VR is more confidential because treatment takes place in the therapist's office. It is also less time consuming as it takes place in the therapist's office. Considering the wide number of situations and activities that agoraphobic patients use to avoid, VR can save time and money significantly. Another advantage in treating PDA using VR is the possibility of doing VR interoceptive. VR could be a more natural setting for interoceptive exposure than the consultation room because we can elicit bodily sensations while the patient is immerse in VR agoraphobic situations. Finally, we think that VR exposure can be a useful intermediate step for those patients who refuse in vivo exposure because the idea of facing the real agoraphobic situations is too aversive for them. In this chapter we offer the work done by our research team at the VEPSY-UPDATED project. We describe the VR program we have developed for the treatment of PDA and we summarize the efficacy and effectiveness data of a study where we compare a cognitive-behavioral program including VR for the exposure component with a standard cognitive-behavioral program including in vivo exposure and with a waiting list control condition. Our findings support the efficacy and effectiveness of VR for the treatment of PDA.

Agoraphobia↗

PubMed2005

[Primary sensory neurons in the central nervous system].

This paper summarizes the results of author's personal observations and the literature data on exteroceptive and some interoceptive neurons of the brain and spinal cord, such as Hesse's intraspinal ocelli, light-sensitive epiphyseal and ependymal neurons. Also described are the light-sensitive ganglion neurons of invertebrates, true bipolar sensory neurons inside the spinal cord, primary chemo- and thermosensitive neurons and sensory unipolar neurons, accompanying four thin Motavkin "central nerves", perforating spinal cord meninges and terminating with bush-like receptors near blood vessels or close to canalis centralis ependyma. The data on all known vertebrate intracerebral and intraspinal interoceptors are summarized in a unified scheme. The hypothesis is formulated, according to which animal and human central nervous system possesses its own sensory innervation, comparable to that one of the other organs, and contains local primary sensory neurons and their asynaptic dendrites, which may be divided into two groups: interoceptive and exteroceptive.

Animals↗

PubMed1991

Eating disorder symptoms in affective disorder.

Patients with Major Affective Disorder (MAD), Secondary Depression, Panic Disorder, and bulimia with and without MAD, were given the Eating Disorder Inventory, the Beck Depression Inventory, and the General Behavior Inventory at presentation. It was found that patients with MAD have a triad of eating disorder symptoms: a disturbance in interoceptive awareness, the sense of ineffectiveness, and a tendency toward bulimia. The data supported the concept that the sense of ineffectiveness is secondary to major depression. A disturbance in interoceptive awareness exists independently in bulimia nervosa and in MAD providing a common diathesis from which bulimia may arise given family and social pressure. Bulimics with MAD do not respond to treatment as readily as those without MAD. It is recomended that these two groups be treated separately.

Adult↗

PubMed1990

Late EEG after-effects in humans following hyperventilation. I. A comparison between intero- and exteroceptive influences.

Using a modification of the computer period analysis of the EEG (Aladjov and Daskalova 1987) we studied the late after-effects (until the 30th min) in human EEG (monopolar leads at F1, C3, P3 and 01) following two kinds of influences: a) short interoceptive one: 3 min hyperventilation (HV) and b) a series of 5 trains of visual light flashes (VS), presented in 5-7 min intervals. The changes in the ongoing EEG in the 2nd min after each VS and in intervals of 5 min after HV were compared with the values before the stimulation. VS did not elicit long-lasting EEG after-effects, which characterized the single interoceptive influence (HV) and consisted mainly of beta-2 (24-36 Hz) EEG activity increase in all studied cortical regions (Nikolov and Kisselkova 1988). Moreover, the exteroceptive stimulation (VS) had no essential influence on the late EEG after-effects after HV, when both kinds of stimulation were applied in the same experiment.

Adult↗

PubMed1990

Effects of cholecystokinin, d-amphetamine and fenfluramine in rats trained to discriminate 3 from 22 hr of food deprivation.

Attempts to assess similarities between the interoceptive stimuli of anorectic drugs and food satiation have generally been limited to human verbal reports. The purpose of the present study was to develop a procedure for assessing similarities between the interoceptive stimuli of food in the gut and various drugs known to alter food intake in rats. Rats (n = 23) were trained in a two-lever, food-reinforced, discrimination paradigm to press one lever when deprived of food for 3 hr and another lever when deprived of food for 22 hr. Criteria for stimulus control over responding were achieved after a mean of 92 (range = 26-175) training sessions. In time course tests, rats were tested when 22, 12, 6 and 3 hr food-deprived. As the number of hours of food deprivation decreased, the percentage of responses that occurred on the 3-hr food deprivation lever increased. In substitution tests, rats that were 22-hr food-deprived consistently responded as if they were 3-hr food deprived after administration of sweetened condensed milk preloads or cholecystokinin, but only occasionally after administration of water preloads, LiCl, d-amphetamine or fenfluramine. These results demonstrate that the presence of food in the gut can function as a discriminative stimulus to control lever choice in rats. Furthermore, they suggest that the discriminative stimulus effects of cholecystokinin, but not d-amphetamine or fenfluramine, are similar to those of food in the gut, and support the hypothesis that cholecystokinin plays a role in the regulation of food intake.

Animals↗

PubMed1988

Experimental assessment of drug-induced changes in cognitive function: vasopressin as a case study.

Two important forms of cognition are knowledge about internal states and social cognition. Knowledge about internal states is dependent on the ability to discriminate between different classes of visceral sensations and to associate them specifically to distinctive cues. The phenomenon of conditioned taste aversion (CTA) is the best example of this type of knowledge. Many chemicals induce interoceptive changes that can be perceived by animals and give rise not only to subjective sensations but also to causal attributions. However, the possibility that animals are able to discriminate different forms of interoceptive changes in a CTA paradigm has received little attention. Studies of the mechanisms of vasopressin-induced CTA provide evidence that it is the case and that animals are able to classify in different categories sensations related to the vasopressor activity of vasopressin and sensation induced by a prototypical aversive drug, apomorphine. Social cognition involves what individuals know about each other. One of the requirements for social cognition is social recognition, i.e., the ability to identify other individuals and classify them in different categories. Social recognition can be assessed by changes in duration of investigation of another animal when the stimulus animal is presented at different intervals. This form of memory is based on olfactory characteristics of the stimulus animal in rats and it can be enhanced or attenuated by memory-modulating drugs, as demonstrated by experiments with vasopressin.

Cognition↗

PubMed1985

[The effect of various ventilation conditions on evoked potentials of the visual cortex of the cat in distention of the stomach].

In 10 cats anaesthetized using chloralose and with muscular relaxation by gallamine and continuous artificial ventilation in acute experiments photically evoked potentials (PEP) were recorded from the visual area of the cortex under different intragastric pressures and varying tidal volumes. It was the aim of this study to examine whether an exteroceptive stimulus (light flash) in the visual analyzer, which is influenced by an interoceptive stimulation (gastric pressure), may also be modified by different tidal volumes. Times, amplitudes and slope parameters, blood pressure and heart rate of the animals were studied. The PEP of the visual cortex was modified under the influence of the interoceptive stimuli. It could, however, be shown that already hypo- and hyperventilation alone may cause alterations in the latency period of the PEP. They arise in a different manner in individual parts of the measured parameters of the PEP and do not change these values in a typical manner. Additional dilatation of the stomach may suppress the phenomena caused by alterations in the tidal volume. Thus, attention should be paid to both blood gases and acid base balance in animals in studies on viscero-cerebral interrelationships as well as to interactions between different analyses using the method of evoked potentials.

Animals↗

PubMedDate not supplied

Some remarks on the nosology of anxiety states and panic disorders.

It is argued that the panic attacks characteristic of anxiety neurosis may be elicited by interoceptive stimuli. The feared sensations are usually associated with anxiety and anxiety neurosis can be conceptualised as a phobophobia. Behavioral research and theory suggest that exposure to the feared interoceptive sensations is the treatment of choice for phobophobics. Reports of successful interventions are discussed.

Anti-Anxiety Agents↗

PubMed1982

Classification of narcotics on the basis of their reinforcing, discriminative, and antagonist effects in rhesus monkeys.

Drug discrimination and drug reinforcement procedures were used to classify a variety of narcotic agonists, mixed agonist-antagonists, and antagonists in the rhesus monkey. A five-way classification was formed. Morphine-like agonists were compounds that shared the capacities to reinforce responding, to produce discriminative stimulus effects similar to those of morphine, and to suppress withdrawal in morphine-dependent rhesus monkeys. Morphine-like mixed agonists-antagonists were differentiated from pure agonists primarily by their capacity to elicit abstinence signs in morphine-dependent monkeys. A third class of narcotic agonists had ethylketazocine as a prototype. These compounds shared a distinctive set of interoceptive stimuli, failed to maintain significant responding relative to morphine-like agonists, and neither suppressed nor elicited withdrawal in morphine-dependent rhesus monkeys. The ethylketazocine-like mixed agonist-antagonists were similar to the ethylketazocine-like agonists, except that they shared the capacity to precipitate a morphine withdrawal syndrome. Narcotic antagonists (e.g., naltrexone) did not share interoceptive effects with either morphine or ethylketazocine, but were able to block the discriminative effects of both types of agonists. Furthermore, narcotic antagonists induced narcotic abstinence in morphine-dependent rhesus monkeys. The present classification scheme may be useful in identifying the properties of new narcotics, for clarifying relationships between narcotics and other pharmacological classes, and in comparing classifications based on other effects of narcotics.

Animals↗

PubMed1994

[Heart beat perception in patients with psychosomatic disorders: distracting attention from personal physical processes].

Based on considerations about the concept of alexithymia as well as from the Theory of Objective Self-Attentiveness the hypothesis was derived that in comparison with "healthy" persons in a control group persons showing psychosomatic disturbances should have a significantly worse perception of their own cardiac action. This poorer capability of perception has been assumed to be the result of the psychosomatic clients actively averting their attentiveness. These assumptions were checked experimentally with the aid of two measuring methods and could be confirmed. A comparison of the accuracy of interoceptive and exteroceptive perception has lead to the conclusion that the lesser degree of perception found with psychosomatic patients does not stem from disturbances of interoceptive processes but is rather the result of these persons actively turning away their attentiveness.

Adult↗