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PubMed1983

Treatment of phobophobia by exposure to CO2-induced anxiety symptoms.

It is argued that fear of fear, or phobophobia, can be an important maintaining factor in cases of seemingly free-floating anxiety with periodic panic attacks and that effective treatment consists of exposure to the feared neurovegetative sensations. The case history presented suggests that inhalation of CO2-O2 mixtures induces the phobic interoceptive sensations and that it can be used in the exposure treatment of phobophobia.

Adult↗

PubMed1998

Impulsive and compulsive self-injurious behavior in bulimia nervosa: prevalence and psychological correlates.

A specific link between self-injurious behavior and bulimia nervosa has been observed. In affective spectrum disorders, some authors propose a distinction between impulsive and compulsive self-injurious behavior. One of the aims of the present study is to examine how different kinds of self-injurious behavior, including purging behavior, may be classified in bulimia nervosa. The clinical impact of the different types of self-injury will be studied. The subjects of the study were 125 consecutive patients with bulimia nervosa, diagnosed by DSM-IV criteria. Subjects were evaluated by means of a semistructured interview and self-report questionnaires (Eating Disorders Inventory and Hopkins Symptom Checklist). In our sample, the distinction between compulsive and impulsive self-injurious behavior appeared to be confirmed by a principal component analysis. Self-induced vomiting loaded on the compulsive dimension and laxative abuse on the impulsive dimension. To study the clinical impact of the two kinds of behavior, bulimic subjects were divided according to their position in the two dimensions. The presence of impulsive self-injurious behavior is associated with a history of sexual abuse and with higher scores on the Symptom Checklist. The presence of both impulsive and compulsive behavior is associated with greater depression, whereas the presence of impulsive features in the absence of compulsive ones seems to be linked to a longer duration of illness and to a higher dropout rate. Both compulsive and impulsive self-injurious behaviors are associated with a greater lack of interoceptive awareness.

Adolescent↗

PubMedDate not supplied

Comparison between weight-preoccupied women and anorexia nervosa.

Psychological traits of patients with anorexia nervosa (AN) were compared to those of weight-preoccupied (WP) and not-weight-preoccupied ( NWP ) women drawn from samples of college and ballet students. Weight-preoccupied subjects were selected on the basis of extreme scores on the Drive for Thinness subscale of the Eating Disorder Inventory ( EDI ). Results indicated that the WP and AN groups were best differentiated by Ineffectiveness, Interpersonal Distrust, and lack of Interoceptive Awareness subscales. Using cluster analysis procedures, weight preoccupied women were divided into two subgroups. Cluster One was characterized by elevated scores on all EDI subscales indicating significant psychopathology. Cluster Two had elevated scores only on Drive for Thinness, Body Dissatisfaction, and Perfectionism and could be described as "normal dieters." These findings were interpreted as indicating that, although there are some highly weight-preoccupied females who display psychopathology quite similar to anorexia nervosa, others only superficially resemble patients suffering from serious eating disorders. These results underscore the importance of a multidimensional evaluation of psychopathology in those suspected of anorexia nervosa.

Adolescent↗

PubMedDate not supplied

Effects of yohimbine on cerebral blood flow, symptoms, and physiological functions in humans.

OBJECTIVE: Increases in adrenergic activity are associated with stress, anxiety, and other psychiatric, neurological, and medical disorders. To improve understanding of normal CNS adrenergic function, CBF responses to adrenergic stimulation were determined. METHODS: Using PET, the CBF changes after intravenous yohimbine, an alpha2-adrenoreceptor antagonist that produces adrenergic activation, were compared with placebo in nine healthy humans. Heart rate, blood pressure, Paco2, plasma catecholamines, and symptom responses were also determined. RESULTS: Among nonscan variables, yohimbine produced significant symptom increases (including a panic attack in one subject), a decrease in Paco2 due to hyperventilation, increases in systolic and diastolic blood pressure, and a trend toward a significant norepinephrine increase. Among scan results, yohimbine produced a significant decrease in whole-brain absolute CBF; regional decreases were greatest in cortical areas. Medial frontal cortex, thalamus, insular cortex, and cerebellum showed significant increases after normalization to whole brain. Medial frontal CBF change was correlated with increases in anxiety. A panic attack produced an increase instead of a decrease in whole-brain CBF. Factors potentially contributing to the observed CBF changes were critically reviewed. Specific regional increases were most likely due in large part to activation produced by adrenergically induced anxiety and visceral symptoms. CONCLUSIONS: This study supports the relationship of anxiety and interoceptive processes with medial frontal, insular, and thalamic activation and provides a baseline for comparison of normal yohimbine-induced CNS adrenergic activation, adrenergically-based symptoms, and other markers of adrenergic function to stress, emotion, and the adrenergic pathophysiologies of various CNS-related disorders.

Adrenergic alpha-Antagonists↗

PubMed1992

Further characterization of adjunctive behavior generated by schedules of cocaine self-administration.

Rhesus monkeys (n = 5), surgically implanted with double-lumen catheters, were allowed to self-administer cocaine (0.1 or 0.3mg/kg/injection, i.v.) on one lever (COC lever) under several fixed-interval schedules of reinforcement. Responding on a second lever (SAL lever) delivered saline (i.v.) under a fixed-ratio 1 schedule. Responding on both levers was a bitonic function of interval value and cocaine dose. A variety of experimental conditions were examined to determine whether SAL lever responding could be considered to be adjunctive in nature. SAL lever responding did not change when saline injections were discontinued, suggesting that SAL lever responding was not maintained by interoceptive stimuli associated with the injection. Discontinuation of various exteroceptive stimulus changes that had occurred as a consequence of SAL lever responding also did not affect the frequency of SAL lever responding. However, when there was no stimulus change following a SAL response, response rates on that lever decreased by approximately 40-60% indicating that stimulus change played some role in the maintenance of the behavior. The introduction of change-over-delays (2-16 s) between responding on the SAL and COC levers had little or no effect on responding on the SAL lever, suggesting that SAL lever responding was not maintained by adventitious reinforcement by cocaine injections. SAL lever responding also occurred in these same monkeys when cocaine was available under fixed-time or variable-interval schedules of reinforcement. These results confirm that presentation of cocaine under interval schedules of reinforcement can generate substantial amounts of behavior (pressing the SAL lever) that is not necessary for obtaining the drug. Further, the results strongly suggest that the behavior can be classified as an adjunctive behavior that is similar to adjunctive behaviors generated by the intermittent presentation of other positive reinforcers.

Journal Article↗

PubMed1997

Assessment of the multiple discriminative stimulus effects of ethanol using an ethanol-pentobarbital-water discrimination in rats.

Previous drug discrimination studies have elucidated the importance of gamma-aminobutyric acidA (GABAA), N-methyl-D-aspartate (NMDA) glutamate, and serotonin (5-HT) receptor systems in mediating the discriminative stimulus effects of ethanol. The present study used a three-choice operant drug discrimination procedure in an attempt to determine if salient GABAergic effects could be separated from other stimulus effects of 2.0 g/kg ethanol. Adult male Long-Evans rats (n = 7) were trained to discriminate pentobarbital (10.0 mg/kg; intragastrically (i.g.) from ethanol (2.0 g/kg; i.g.) from water (4.7 ml; i.g.) using food reinforcement. Stimulus substitution tests were conducted following the administration of allopregnanolone (1.0-17.0 mg/kg; intraperitoneally (i.p.)), diazepam (0.1-7.3 mg/kg; i.p.), midazolam (0.0056-17.0 mg/kg; i.p.), dizocilpine (0.01-0.56 mg/kg; i.p.), phencyclidine (1.0-5.6 mg/kg; i.p.), CGS 12066B (3-30 mg/kg; i.p.), RU 24969 (0.1-5.6 mg/kg; i.p.) and morphine (1 or 3.0 mg/kg; i.p.). Within the group, allopregnanolone and midazolam completely substituted (> 80%), and diazepam partly substituted (67%) for the discriminative stimulus effects of pentobarbital. Dizocilpine and phencyclidine partly substituted (58 and 57%, respectively) for ethanol without substantial pentobarbital-appropriate responding. RU 24969, CGS 12066B and morphine did not result in complete substitution for either ethanol or pentobarbital, although RU 24969 resulted in partial (68%) pentobarbital substitution. The ability to train the present three-choice discrimination in rats indicates that the discriminative stimulus effects of 10.0 mg/kg pentobarbital were separable from those of 2.0 g/kg ethanol. The results suggest that the pharmacological effects of ethanol, which can control behavior, may seemingly be modified by training conditions (two-versus three-choice discrimination procedures), to the extent that a receptor system prominently linked to the behavioral activity of ethanol (i.e. GABAA) appears no longer to be involved in the interoceptive effects of the drug.

Animals↗

PubMed1998

The discriminative stimulus effects of clomethiazole in the rat.

Rats were trained in a two-lever drug discrimination procedure using saline or clomethiazole (8 mg/kg, s.c. 15 min) as the training stimuli. A criterion of 9/10 days correct lever choice was adopted to select rats for substitution tests. The clomethiazole (CMZ) cue was not especially strong, and stable performance at this level was not achieved consistently. Nevertheless, in a series of substitution tests carried out in extinction, diazepam (3 mg/kg), chlordiazepoxide (10 mg/kg), phenobarbital (60 mg/kg), dizocilpine (0.1 mg/kg) and mianserin (3.0 mg/kg) were found to substitute for the training dose of CMZ. The first two of these produced a percentage choice of the drug lever equal to that produced by the training dose of CMZ (full generalization) whereas the latter three produced only partial generalization. Ethanol, muscimol, allopregnanolone, chlorpromazine and amitriptyline did not generalize to CMZ. CMZ is known to potentiate gamma-aminobutyric acid (GABAA) receptor function, a finding supported by the generalization to CMZ of the two benzodiazepines and phenobarbital. However, not all drugs acting at GABAA receptors generalized to CMZ. Although CMZ has no affinity for the N-methyl-D-aspartate (NMDA) receptor, it antagonizes a number of pharmacological responses mediated by NMDA receptors. The generalization in the drug discrimination procedure reported here support the suggestion that altering GABA activity can modulate NMDA-mediated responses. The lack of generalization after treatment with ethanol, chlorpromazine and amitriptyline suggests that the interoceptive cues are not mediated by a generalized sedation or drug-induced motor impairment.

Animals↗

PubMed1998

Discriminative stimulus properties of the atypical neuroleptic clozapine in rats: tests with subtype selective receptor ligands.

The interoceptive stimulus induced by clozapine (5 mg/kg, i.p.) has been characterized in an operant drug discrimination procedure in the rat using a wide range of receptor subtype-selective agonists and antagonists. Only the muscarinic receptor antagonist scopolamine generalized fully to clozapine (>80%). Partial generalization (defined here as 40% maximal generalization) was seen with the D1 receptor antagonist SCH 23390 (43% maximal generalization), the alpha1-adrenoceptor antagonist prazosin (67%) and the alpha2-adrenoceptor antagonist methoxyidazoxan (42%). All other specific agents tested induced <25% maximal generalization, including the alpha2-adrenoceptor antagonist yohimbine (24%), the histamine H1 receptor antagonist mepyramine (21%), the D2 antagonist typical neuroleptic haloperidol (23%), the D4 receptor antagonist L-745,870 (14%), the 5-hydroxytryptamine-1A (5-HT1A) receptor agonist S-14506 (8%), the 5-HT2A receptor antagonists ketanserin (0%) and M100907 (12%), the 5-HT2B/2C receptor antagonists SB 200646A (8%) and SDZ SER 082 (6%), and the 5-HT3 receptor antagonist ondansetron (0%). The clozapine discriminative stimulus was not blocked by the dopamine D1 receptor antagonist SCH 23390, or by the 5-HT1A receptor antagonist WAY 100635, when given concomitantly with clozapine. Although the results suggest that muscarinic antagonism plays a major role in the clozapine cue, the results have to be considered in the light of the full generalization to clozapine seen with various antipsychotic agents which have very low affinity for muscarinic receptors, including zotepine, quetiapine, JL13 and PNU 96415 (a finding replicated in rats from the same breeding colony as those which generalized to scopolamine). Thus, generalization to clozapine for antipsychotics with multiple affinities but with low muscarinic affinity is probably mediated by additive or perhaps supra-additive actions at other receptors, although extensive studies with various combinations of drug mixtures are required to validate this hypothesis.

Adrenergic alpha-Antagonists↗

PubMed1999

An investigation of endogenous neuroactive steroid-induced modulation of ethanol's discriminative stimulus effects.

Neuroactive steroids exhibit rapid non-genomic central nervous system activity, including modulation of GABAA and NMDA receptors, two receptors known to mediate the effects of methanol. Neuroactive steroids that modulate GABAA receptors in a manner similar to ethanol were expected to potentiate the discriminative stimulus and/or rate-suppressing effects of ethanol. In contrast, neuroactive steroids that modulate GABAA or NMDA receptors in a manner opposite to ethanol were hypothesized to attenuate the effects of ethanol. Adult male rats were trained to discriminate 1.0 or 2.0 g/kg ethanol (i.g.) from water (i.g.). Animals were pretreated with subthreshold doses (i.p.) of ethanol and neuroactive steroids and exposed to an acute stressor (n = 5), prior to conducting ethanol cumulative-dosing (i.p.) tests. Only ethanol and 3 beta, 5 beta-P pretreatments potentiated the discriminative stimulus effects of ethanol. None of the six neuroactive steroid manipulations attenuated the effects of ethanol. These results demonstrate that a neuroactive steroid, endogenous in humans, can enhance the interoceptive effects of ethanol.

Alcohol Drinking↗

PubMed2006

Effects of dose and time on the ability of alcohol to prime social drinkers.

Interoceptive drug cues, through associations with the drug's reinforcing properties, may act as conditioned stimuli and elicit conditioned responses. For instance, a dose of alcohol, given to alcohol-experienced people, can lead to an enhancement of alcohol drinking, a phenomenon known as the priming effect. The present study aimed to investigate the alcohol priming effect in non-dependent social drinkers with respect to the dose of alcohol preload and the time of testing after preload. Fifteen social drinkers participated in five daily consecutive sessions. On days 1 and 2 (training sessions), participants consumed a 500 ml beverage of either 0.6 g/kg of alcohol or placebo (50 ml aliquots) presented in 10 colour-coded cups. During days 3, 4 and 5 (testing sessions), a preload of placebo, 0.3 or 0.6 g/kg of alcohol was given (in randomized sequence) in 10 opaque colourless cups. Thirty, 60 and 90 min following the preload, participants responded to an imagery script referring to the drinks sampled at training including a question on the number of aliquots participants would consume from each of the drinks if given the opportunity (hypothetical choice). Participants completed questionnaires evaluating mood and alcohol desires at baseline (before the beverages were given) and after the hypothetical choice. The hypothetical choice showed significant interactions between dose and time: the greatest number of alcohol aliquots were wanted 30 min following the 0.6 g/kg dose of alcohol preload. Ratings from the Desires for Alcohol Questionnaire also showed that alcohol desires peaked 30 min following the 0.6 g/kg of alcohol preload. These data support previous evidence that priming with alcohol can occur and indicate that dose of, and time after preload might affect the strength of, the priming effect for alcohol-related behaviours.

Adult↗

PubMed2005

Meditation experience is associated with increased cortical thickness.

Previous research indicates that long-term meditation practice is associated with altered resting electroencephalogram patterns, suggestive of long lasting changes in brain activity. We hypothesized that meditation practice might also be associated with changes in the brain's physical structure. Magnetic resonance imaging was used to assess cortical thickness in 20 participants with extensive Insight meditation experience, which involves focused attention to internal experiences. Brain regions associated with attention, interoception and sensory processing were thicker in meditation participants than matched controls, including the prefrontal cortex and right anterior insula. Between-group differences in prefrontal cortical thickness were most pronounced in older participants, suggesting that meditation might offset age-related cortical thinning. Finally, the thickness of two regions correlated with meditation experience. These data provide the first structural evidence for experience-dependent cortical plasticity associated with meditation practice.

Adult↗

PubMed2006

Association of catecholamine-O-methyltransferase and 5-HTTLPR genotype with eating disorder-related behavior and attitudes in females with eating disorders.

OBJECTIVE: There is growing evidence, that genetic variants contribute to the pathogenesis of anorexia nervosa and bulimia nervosa. Genetic studies have revealed candidate genes, but no satisfactory associations with the disorders have been found so far. The aim of the present study was to evaluate, whether behavioral and attitudinal traits of the disorders can serve as phenotypes with a possible association with two common functional polymorphisms of the monoaminergic pathways. METHOD: Forty-five female in-patients of a specialized hospital for eating disorders were included into the study. Eating disorder symptomatology was assessed using the Eating Disorder Inventory-2. The functional catecholamine-O-methyltransferase (COMT) 158 Val-->Met polymorphism and the deletion/insertion polymorphism of the serotonin transporter promoter 5-HTTLPR were determined. RESULTS: Carriers of at least one Met-allele of the COMT gene had significantly higher total scores of the Eating Disorder Inventory-2, as well as significantly higher scores on the subscales bulimia, ineffectiveness, interoceptive awareness, maturity fears and impulse regulation. Carriers of the deletion of the 5-HTTLPR had significantly higher scores on the subscales drive for thinness and body dissatisfaction. CONCLUSION: We found associations between the COMT and the 5-HTTLPR polymorphisms and specific clinical, behavioral and attitudinal traits of eating disorders. These polymorphisms may predispose their carriers to exhibit certain symptoms of eating disorders or confer a general risk for more severe forms of these disorders.

Adolescent↗

PubMedDate not supplied

Remembering and forgetting as context discrimination.

In 1929, H.C. Blodgett reported the results of a seminal maze learning experiment using rats. In that experiment, hungry rats ran in a complex maze but were not rewarded on reaching the goal box. Not surprisingly, the performance of the hungry rats did not improve over trials. However, with the introduction of reward, the error scores of the rats suddenly dropped to the level of the control rats that were rewarded from the outset. This finding indicates that the experimental group had learned the maze despite the absence of reward but that the learning was latent rather than manifest. With Blodgett's findings, the distinction between learning and performance became firmly established, if not as widely appreciated as it might be. Blodgett's (1929) early experimental finding of latent learning could well serve as a paradigm for the approach taken here. That is, we have emphasized the principle that a lack of performance does not necessarily indicate a lack of either learning or memory. This principle is much more than an empty admonition: We have shown it can have a firm theoretical basis, one that has been confirmed repeatedly by experiments cited throughout this paper. That is, it has been shown numerous times that a failure to perform either in a Pavlovian or instrumental learning task or to remember in an animal or human memory task under one set of conditions could be alleviated under another set of conditions. Forgetting was viewed here as a failure of performance resulting from the cues at test retrieving a memory other than the target memory or retrieving no memory at all. According to this view, memory involves discrimination learning. Essentially, memories are stored in the presence of an elaborate set of interoceptive and exteroceptive stimuli, a context. Whether at test the target memory is retrieved depends on how well the cues at test discriminate between the target memory and other memories. This approach suggests that forgetting does not occur: There is only a failure to perform because of a difference between the stimulus conditions prevailing at encoding and at test. It was demonstrated that this approach is at least as reasonable as that which suggests that true forgetting occurs, but certainly more useful. At least three advantages adhere to our view that memory is a discrimination problem. First, in almost numberless cases, it has been shown that failure of performance under one set of stimulus conditions can be alleviated under some other set of stimulus conditions. Second, the proposition that altered stimulus conditions are responsible for forgetting is one of wide generality. Thus, the altered stimulus conditions approach can serve as an explanation not only for various human memory findings but also for various animal memory and learning findings. Finally, and perhaps most importantly, the present approach provides investigators with a powerful and proven working hypothesis. It tells us not to accept failures of performance as indicating an absence of learning or a loss of memory but rather to seek conditions favorable to improving performance, a strategy that should lead to a better fundamental understanding of memory and learning. This position is obviously a type of optimality theory, of which evolutionary theory is one of the more outstanding examples. In optimality theory, any deviation from some ideal state or condition prompts the investigator to seek the reasons for deviation. This approach may prove as successful when applied to learning and memory as it has to other areas of science.

Animals↗

PubMed2005

Formalin attenuates the stress-induced increase in plasma epinephrine levels.

Subcutaneous (s.c.) injection of formalin into rats is frequently used as a painful stressor that produces a three-phase nociceptive response. We have shown previously that s.c. administered formalin (0.2 ml of 4% solution per 100 g body weight) unexpectedly attenuated the increase of plasma epinephrine levels in rats exposed to exteroceptive stressors (handling, immobilisation). To clarify the mechanism(s) responsible for this phenomenon, the effect of formalin applications on epinephrine plasma levels was investigated in various experimental conditions. Subcutaneous application of formalin combined with exposures of animals to an interoceptive stressor, insulin-induced hypoglycaemia, significantly attenuated the stress-induced increase in plasma epinephrine levels, whereas plasma norepinephrine levels remained highly elevated. Moreover, administration of formalin to unstressed animals also manifested signs of an attenuated epinephrine secretion. Interestingly, intraperitoneal administration of formalin did not reduce the elevated levels of plasma epinephrine. We suggest that formalin attenuates epinephrine secretion from the adrenal medulla most probably via irritation of s.c. somatosensory receptors. We hypothesise that the irritation of the primary sensory afferents fibres might reduce the activity of the sympathetic preganglionic neurones innervating adrenal medullary chromaffin cells. Further investigations are required to establish whether the observed reduction of epinephrine secretion from the adrenal medulla is controlled by either spinal or supraspinal neuronal circuits.

Animals↗

PubMed1993

On the relation between cardiodynamics and heartbeat perception.

The mediation of heartbeat perception by cardiodynamic parameters was investigated by experimentally introducing changes in heart performance. Twenty-five subjects (14 women, 11 men) underwent bicycle ergometric exercises (0-75 W) at different tilt angles (90 degrees-0 degree). After each of the 31 tilt/exercise phases, the following measures of cardiac performance were taken using impedance cardiography: stroke volume, Heather Index (as an indicator of contractile force), heart rate, and an estimate of the momentum of the ejected blood mass. Additionally, a heartbeat perception task was performed. The different tilt/exercise combinations induced profound changes in all cardiodynamic measures. The correlation between heartbeat perception and cardiodynamic parameters was highest for "momentum" (r = .67) and for stroke volume (r = .59). From our data, we infer that intraindividually occurring changes in cardiac perception are mediated partially by characteristics of heart dynamics and that the source of these interoceptive signals lies in the heart or in its close vicinity.

Adult↗

PubMed1990

Evidence against an involvement of the haloperidol-sensitive sigma recognition site in the discriminative stimulus properties of (+)-N-allylnormetazocine ((+)-SKF 10,047).

1. The involvement of the haloperidol-sensitive, sigma recognition site and the N-methyl-D-aspartic acid (NMDA) receptor in the mediation of the discriminative stimulus properties of (+)-N-allylnormetazocine [+)-NANM, (+)-SKF 10,047), has been investigated in the rat by use of a two-lever, operant drug discrimination paradigm. 2. Six compounds with nanamolar affinity for the sigma recognition site [+/-)-pentazocine, (+)-3-(hydroxyphenyl)-N-propylpiperidine [+)-3-PPP), ditolylguanidine (DTG), haloperidol, (-)-butaclamol and BMY 14802) were investigated for their ability to generalise or antagonise the (+)-NANM discriminative stimulus. Each drug was tested at doses found in an ex vivo radioligand binding assay to displace [3H]-DTG from the central sigma recognition site by more than 40%. 3. While (+/-)-pentazocine (in the presence of naloxone) generalised and (+)-3-PPP partially antagonised the (+)-NANM cue, the other putative sigma ligands were ineffective either as agonists or antagonists at doses clearly occupying the sigma site in vivo. 4. Dose-dependent generalisation to the (+)-NANM cue was seen with the selective non-competitive NMDA receptor antagonist, MK-801, a compound devoid of significant affinity for the sigma recognition site. 5. (+/-)-Pentazocine was found to antagonise seizures induced in the mouse by NMDLA, a model reflecting antagonism of central NMDA receptors, and a strong correlation was found between the rank order of potency of compounds to generalise to the (+)-NANM discriminative stimulus and their potencies as anticonvulsants. 6. In conclusion, no evidence was found to substantiate the contention that the discriminative stimulus properties of (+)-NANM are mediated by the haloperidol-sensitive sigma recognition site. On the other hand, the results are consistent with the interoceptive stimulus being mechanistically based in the NMDA receptor complex.

Animals↗

PubMed1993

State-dependent stimulus control: cueing attributes of ethanol "hangover" in rats.

In Experiment 1, twelve Sprague-Dawley rats were trained in a two-choice food-reinforced drug discrimination task (10-min sessions) using the state-dependent interoceptive stimulus attributes of ethanol's (ETOH) delayed or rebound effects (EDE) versus "normal" basal homeostasis. Rats were injected with either 4 g/kg ETOH or equivalent volumes of saline (SAL) 18 hr before the sessions. Each rat was injected with an additional 1 ml/kg injection of SAL 15 min before the sessions. EDE training sessions were always followed by a "day off." SAL sessions were conducted between 36-96 hr after an EDE training session. Rats demonstrated > 90% discriminative accuracy. Test sessions showed a time-dependent, cyclic, return from the experimental "hangover" state to the "normal" state, by 48 hr. The acute (immediate) effects of ETOH and chlordiazepoxide (0.75 g/kg or 0.18 mg/kg, respectively; @15 min) did not cross-generalize with the "hangover" state. Both these low-dose ETOH and chlordiazepoxide pretreatments blocked the stimulus attributes of "hangover." All subjects responded on the EDE-appropriate lever at 5.6 mg/kg pentylenetetrazole and exhibited an increase in susceptibility to clonic seizures. In Experiment 2 blood alcohol concentration kinetics functions were quantified in three groups (n = 8/group) of age-matched cohorts to Experiment 1 subjects (2, 3, and 4 g/kg ETOH) using a head-space gas chromatographic technique. The training stimulus state associated with 4 g/kg, at 18 hr postinjection intervals, in Experiment 1, did not produce any chromatogram peaks for ETOH or any its active metabolite (acetaldehyde, acetone, nor methanol).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

Role of the amygdala in decision-making.

The somatic marker hypothesis proposes that both the amygdala and the orbitofrontal cortex are parts of a neural circuit critical for judgment and decision-making. Although both structures couple exteroceptive sensory information with interoceptive information concerning somatic/emotional states, they do so at different levels, thus making different contributions to the process. We define "primary inducers" as stimuli that unconditionally, or through learning (e.g., conditioning and semantic knowledge), can (perceptually or subliminally) produce states that are pleasurable or aversive. Encountering a fear object (e.g., a snake), a stimulus predictive of a snake, or semantic information such as winning or losing a large sum of money are all examples of primary inducers. "Secondary inducers" are entities generated by the recall of a personal or hypothetical emotional event or perceiving a primary inducer that generates "thoughts" and "memories" about the inducer, all of which, when they are brought to memory, elicit a somatic state. The episodic memory of encountering a snake, losing a large sum of money, imagining the gain of a large sum of money, or hearing or looking at primary inducers that bring to memory "thoughts" pertaining to an emotional event are all examples of secondary inducers. We present evidence in support of the hypothesis that the amygdala is a critical substrate in the neural system necessary for triggering somatic states from primary inducers. The ventromedial cortex is a critical substrate in the neural system necessary for the triggering of somatic states from secondary inducers. The amygdala system is a priori a necessary step for the normal development of the orbitofrontal system for triggering somatic states from secondary inducers. However, once this orbitofrontal system is developed, the induction of somatic states by secondary inducers via the orbitofrontal system is less dependent on the amygdala system. Perhaps the amygdala is equivalent to the hippocampus with regard to emotions, that is, necessary for acquiring new emotional attributes (anterograde emotions), but not for retrieving old emotional attributes (retrograde emotions). Given the numerous lesion and functional neuroimaging studies illustrating the involvement of the amygdala in complex cognitive and behavioral functions, including "social cognition," we suggest that this involvement is a manifestation of a more fundamental function mediated by the amygdala, which is to couple stimuli/entities with their emotional attributes, that is, the processing of somatic states from primary inducers.

Amygdala↗