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PubMed1994

Amygdala pathology in Parkinson's disease.

The amygdala undergoes severe pathological changes during the course of Parkinson's disease (PD). Lewy bodies and Lewy neurites are distributed in a specific manner throughout the nuclear complex. The lesional pattern displays only minor interindividual variation. The most prominent changes occur in the accessory cortical and central nuclei. The cortical, accessory basal and granular nuclei show less severe alterations, while the basal and lateral nuclei, as well as the intercalated cell masses, generally remain uninvolved. The amygdala receives a broad range of afferents, allowing integration of exteroceptive information with interoceptive data. It generates major projections to the isocortex (the prefrontal cortex in particular), limbic system (hippocampus and entorhinal region) and centers regulating endocrine and autonomic functions. The specific lesional pattern seen in PD destroys part of the nuclear gray matter and its connections and, thus, may likely contribute to the development of behavioral changes and autonomic dysfunctions.

Aged↗

PubMed1981

Inter-animal olfactory cues in operant drug discrimination procedures in rats.

Olfactory cues from prior subjects in operant chambers were shown to be an effective stimulus which rodents could use to direct lever selection in a typical operant drug discrimination (DD) paradigm. Such cues persisted for very long periods of time (16 h), and were deposited after very short (5 min) operant sessions. In extinction tests inter-animal olfactory cues exerted very strong stimulus control over lever selection. Furthermore, such cues were not specific to individual rodent subjects but were generalizable between subjects. Inter-animal cues directing level selection could be abolished by cleaning operant manipulanda with a 10% alcohol solution. Reanalysis of some DD data previously reported by one of the authors (Goudie 1977) indicated that this specific earlier study (and by implication perhaps other studies) might have been confounded by inter-animal cues. In a DD study with nicotine it was found that the drug cue was antagonized by mecamylamine for all subjects except those who had a reliable olfactory cue from prior subjects to direct lever selection (subjects who possessed both an olfactory and a drug cue to direct lever selection responded in a way suggesting that the exteroceptive olfactory cue controlled behaviour rather than the interoceptive drug cue). These findings indicate that inter-animal olfactory cues could be of considerable methodological significance in DD studies. The possible significance of such cues has not previously been reported upon in detail, and in reports of many DD studies there do not appear to be explicit indications that inter-animal cues have been adequately controlled.

Animals↗

PubMed1979

Dissociation of autonomic and cognitive effects of THC in man.

Intravenous THC, 30--44.8 microgram/kg, was administered to four subjects. Each received THC on four occasions preceded by either i.v. saline, 0.04 mg/kg atropine sulfate, 0.2 mg/kg propranolol, or both drugs together. Heart rates, subjective intoxication and symptom ratings, time productions, and EEG activity were measured. In the absence of autonomic blocking drugs, THC produced characteristic tachycardia, subjective intoxication, and EEG effects. After combined autonomic blockade, THC had no effect on heart rate, while subjective and EEG changes remained as intense. These findings argue against the hypothesis that the subjective and EEG effects of THC are mediated by autonomic receptors or by interoception of peripheral autonomic actions of THC.

Adult↗

PubMed1984

Differential effects of apomorphine in 6-hydroxydopamine-treated and aged rats.

Effects of dopamine depletion and old age were tested on the ability of rats to discriminate the interoceptive cue produced by IP administered apomorphine. In Experiment 1, rats were administered IC injections of 6-hydroxydopamine or its vehicle at 5 days of age. Administration of this dopamine neurotoxin resulted in significant depletion of whole-brain dopamine to 27.2% of controls as indicated when the brains of littermate rats, killed at 35 days of age, were analyzed by high-pressure liquid chromatography. Although this dopamine depletion was significant, toxin-treated rats learned to discriminate 0.16 mg/kg apomorphine from saline at the same rate as control rats. However, the dose-response curve for apomorphine discrimination after doses of 0.04-0.24 mg/kg suggested hypersensitivity to the dopamine agonist in toxin-treated rats. In Experiment 2, senescent rats were similarly trained to discriminate apomorphine in the two-lever food-motivated operant task. Dose-response testing indicated hypersensitivity similar to that found in 6-OHDA-treated rats. This increased behavioral responsiveness of aged rats to dopamine agonists is discussed in relation to receptor supersensitivity, metabolic rates, and blood-brain barrier permeability.

Aging↗

PubMed1984

Drug effects on the repeated generalization of a visual discrimination acquired under one trial per day conditions.

Six pigeons were trained to respond under concurrent fixed-ratio extinction schedules of food reinforcement (FR 50) on the side keys of a three key chamber. Presence or absence of continuously-flashing, colored lights on the center key signalled which key pecking response (left or right) would be reinforced over the course of an entire experimental session; thus, the lights were analogous to a drug cue in drug-discrimination situations. In test (generalization) sessions of one FR in duration, the percentage of light on the center key was varied from 0 to 100%. During these sessions, saline, lysergic acid diethylamide (LSD; 0.04-0.20 mg/kg) and morphine (3.75 mg/kg) produced orderly, log-linear light generalization gradients, but only LSD shifted the gradient to the right (by approximately 50%). These results demonstrate the potential value of the method for assessing the effects of drugs on both exteroceptive (light) and interoceptive (drug) stimulus control. The method has the additional advantage that the effects of drugs on such control (i.e., on stimulus generalization) are relatively unaffected by corresponding effects on response control (e.g., rate of responding).

Animals↗

PubMed1979

Discriminative stimulus properties of psychomotor stimulants in the cat.

Cats were trained to choose between two levels or an operant chamber using interoceptive cues provided by d-amphetamine or saline as the discriminative stimuli. Following training, stimulus generalization was observed to additional doses of d-amphetamine and cocaine. but not to morphine. Clozapine blocked the generalization of the drug discrimination response to d-amphetamine, but had no effect on generalization to cocaine. These data indicate that discriminative stimulus properties of psychomotor stimulants, previously described in rats, are similar in cats.

Animals↗

PubMed1989

Sensitivity of pentylenetetrazol discrimination increased by a stimulus fading technique.

The interoceptive stimulus produced by pentylenetetrazol (PTZ) is pharmacologically similar to anxiety and is used in a behavioral assay for anxiety-related stimuli (the PTZ model of anxiety). The stimulus fading technique was tested as a method to increase the sensitivity of this assay. Rats were trained with food-reward to press one lever after injection of PTZ and an alternate lever after saline. Rats initially learned the discrimination at a PTZ dose of 20 mg/kg. They were then trained with sequentially lower doses until they reliably discriminated a PTZ dose of 10 mg/kg. Substitution tests with other doses and drugs showed that, after the fading procedure, dose-response curves were shifted to lower doses for PTZ, Ro 5-3663, and nicotine Similarly, the dose of diazepam required to block the low dose of PTZ was lower than that required to block the higher dose of PTZ. These results indicated that the sensitivity of the discrimination was enhanced in rats trained to discriminate a lower dose of PTZ. Doses of nikethamide, cocaine, and yohimbine that did not substitute for the higher dose of PTZ also did not substitute for the lower dose. These data suggest that rats can be trained to discriminate a low dose of PTZ by the stimulus fading technique. Moreover, they suggest that this training method does not compromise the specificity of the discrimination.

Animals↗

PubMed1989

Alcohol consumption following bidirectional shifts in body weight in rats.

Weight restriction has frequently been used to induce consumption of pharmacologically significant amounts of alcohol by rats. When previously weight-restricted rats are fed ad lib., however, their alcohol consumption is substantially reduced. This could occur because weight restriction per se causes increased alcohol consumption, or because the stimulus conditions (in this case, largely interoceptive) that were originally associated with drinking have changed, resulting in a stimulus generalization decrement. The present experiment was designed to discriminate between these two possibilities. Two groups of animals, one at free-feeding weight (FFW) and one at 80% FFW were initially trained to drink alcohol in a limited access paradigm. Each group was then divided into two, such that one half remained at its original weight and the other was gradually shifted to the reverse feeding condition in a double cross-over design. When alcohol consumption was again stable the experimental groups were returned to their original weights. If the weight restriction hypothesis were true, animals should drink more when weight-reduced and less when at FFW. According to the stimulus generalization decrement hypothesis, drinking should decrease with any shift from their initial weight. The direction of the results was such as to support the weight restriction hypothesis, but the magnitude of the changes was greater than would be expected on the basis of the respective control groups, and the effects were often transient. In these ways the results more closely resembled positive and negative contrast effects that have traditionally been described following shifts in amount of reinforcement. Possible mechanisms and the importance of an animal's history as a determinant of alcohol consumption are discussed.

Alcohol Drinking↗

PubMed1992

Effects of the putative dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 on the discriminative stimulus properties of cocaine.

Recent evidence suggests that the putative dopamine (DA) autoreceptor antagonists, (+)-AJ 76 and (+)-UH 232, share some neurochemical and behavioral effects with both psychostimulants and neuroleptics. The ability of (+)-AJ 76 and (+)-UH 232 to mimic or antagonize the stimulus effects of cocaine was investigated in rats trained to discriminate 5 mg/kg (N = 8) or 10 mg/kg (N = 8) of cocaine from saline in a two-lever, water-reinforced, drug discrimination task. In the cocaine (10 mg/kg) group, administration of (+)-AJ 76 (2.5-20 mg/kg) engendered only a partial substitution for cocaine (maximum 60% cocaine-lever responses). Given in combination with cocaine (10 mg/kg), (+)-AJ 76 (2.5-40 mg/kg) did not significantly attenuate the cocaine cue. A fixed dose of (+)-AJ 76 (2.5 or 10 mg/kg) plus various doses of cocaine (1.25-5 mg/kg) did not alter the cocaine dose-response curve. (+)-UH 232 (2-16 mg/kg) produced primarily saline-appropriate responding in rats trained to discriminate 5 mg/kg of cocaine and was unable to block the interoceptive cocaine state when given in combination with cocaine (5 mg/kg). (+)-UH 232 (2 or 8 mg/kg) also did not alter the cocaine dose-response curve. These results suggest that (+)-AJ 76 and (+)-UH 232 elicit only weak or no cocaine-like stimulus effects and, unlike neuroleptics, do not attenuate the cocaine cue.

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

PubMed1993

A behavioural and pharmacological evaluation of the discriminative stimulus induced by pentylenetetrazole in the pig.

The anxiogenic nature of the interoceptive discriminative stimulus induced by pentylenetetrazole (PTZ) was investigated by examining the discriminatory behaviour of PTZ conditioned pigs during a conditioned emotional response (CER). A CER was induced in a nonoperant situation, by pairing a tone stimulus with the application of a mild, non-injurious electric shock. Subsequent presentation of the conditioned tone stimulus alone produced a generalisation to the PTZ cue. This generalisation of the conditioned emotional state (CES) to the PTZ cue was antagonised by pretreatment with diazepam (0.5 mg/kg, PO; 30 min). The PTZ stimulus was also antagonised by diazepam (0.5 mg/kg, PO; 30 min) but not by an anticonvulsant dose of ethosuximide (30 mg/kg, PO; 1-3 h), providing further confirmation of the anxiogenic nature of the PTZ cue. Our results demonstrate the validity of the PTZ discrimination paradigm in pigs as a test of anxiety.

Animals↗

PubMed1995

The discriminative properties of the D1 dopamine agonist dihydrexidine in the rat.

The objective of this study was to train rats to discriminate the interoceptive stimuli produced by a selective dopamine D1 agonist. Fourteen male Sprague-Dawley rats acquired the discrimination of the fully effective, high potency, D1 agonist dihydrexidine (DHX) within 20 sessions using a training dose of 3.0 mg/kg. DHX (0.75-4.5 mg/kg) dose-dependently increased DHX-appropriate responding with an ED50 = 1.44 mg/kg. The selective D1 agonist SKF 38398 (2.0-8.0 mg/kg) dose-responsively generalized with an ED50 = 3.54 mg/kg; significantly less potent than DHX. The selective D1 antagonist SCH 23390 (0.06-0.12 mg/kg) dose-responsively decreased DHX-appropriate discriminative performance. These data would indicate that DHX is a selective D1 agonist that may allow for testing of the selectivity of other putative D1 agonists in this experimental procedure. Administration of non-selective dopaminergically active drugs, including apomorphine, amphetamine and cocaine, were each shown to produce intermediate DHX-appropriate discriminative performance.

Amphetamine↗

PubMed1993

Central alpha-2 adrenoceptors are responsible for a clonidine-induced cue in a rat drug discrimination paradigm.

Clonidine produces an interoceptive discriminative stimulus or "cue" in rat drug discrimination studies. This cue may be mediated by its alpha-2 adrenoceptor agonist properties and/or its affinity for the non-adrenoceptor imidazoline preferring receptor. Six rats were trained to respond differentially after receiving clonidine (0.02 mg kg-1, IP) or a saline vehicle. The alpha-2 adrenoceptor agonists clonidine, UK14, 304 and rilmenidine, which bind to the imidazoline preferring receptor, and guanabenz which does not, dose-dependently substituted for (i.e. > 80% total responding was clonidine associated) the clonidine-induced cue in doses up to 0.02, 0.16, 1.25 and 0.32 mg kg-1, respectively. Furthermore, the cue was blocked when clonidine was given in combination with 30-min pretreatments of the highly selective alpha-2 adrenoceptor antagonists RX811059 (2.5 mg kg-1) and fluparoxan (3 mg kg-1). Since the clonidine-induced cue was substituted for by guanabenz, which does not act at the imidazoline-preferring receptor, and antagonised by RX811059 and fluparoxan it appears to be mediated by alpha-2 adrenoceptors. Moreover, abolition of the clonidine-induced cue did not occur with the peripherally acting alpha-2 adrenoceptor antagonist L659, 066 suggesting it involves central as opposed to peripheral sites.

Adrenergic alpha-2 Receptor Agonists↗

PubMedDate not supplied

Stress and cytokine effects on learning: what does sex have to do with it?

Many studies have alluded to sexually dimorphic changes in behavior following stress. Although many have suggested that these changes are a function of stress-induced changes in learning and memory, there are questions regarding whether performance in those learning and memory tasks are influenced by stress-induced changes in drive more than in actual learning and memory processes. We used the classically conditioned eyeblink response (CCER) to determine whether slowed learning following stress in females can be explained by changes in unconditional response (UR) amplitude, a sign of a stress-induced shift in sensory reactivity. In addition, we had a second treatment group injected with the pro-inflammatory cytokine IL-1beta to serve as an interoceptive stress condition, a physiological stressor with minimal stimulation to the animal. Replicating the work by Shors and colleagues, we found that stressed female rats had slower acquisition of the conditioned response (CR), but we also found that an IL-1beta injection leads to a slowing of CR acquisition. However, in both cases, UR amplitude was lower in the treatment groups. We followed up these results by testing sensory reactivity through the acoustic startle response (ASR), where the magnitude of the ASR was marginally, but nonsignificantly, reduced by the same dose regimen of IL-1beta. Together, these experiments suggest that tailshock stress and immune signaling (IL-1beta) reduce sensory reactivity and the saliency of the stimuli used in the CCER, leading to slower learning in female rats.

Animals↗

PubMed2005

Eating disorder variables and self image in Italian girls attending a weight control clinic.

OBJECTIVE: The aim of this study was to evaluate eating disorder variables and self image in Italian female adolescents asking for a weight control treatment. METHOD: Eating Disorder Inventory-2 (1991) and Offer Self-Image questionnaire (1989) were administered; 100 subjects (75 outpatients and 25 controls) were enrolled over a period of three months and divided into three study groups (normal, overweight and obese), and one control group. RESULTS: The relationship between BMI and problematic personality traits tends to be linear and positive. Obese adolescent females describe themselves in more negative terms than non-obese individuals and show a psychological profile similar to individuals with eating disorders, especially for Drive for Thinness and Interoceptive Awareness. Even in the absence of overt mental pathology, obesity can result associated to a psychological distress and it's a risk factor for mental health.

Adolescent↗

PubMed2006

Eating disorder traits in obese children and adolescents.

The aim of the present study was to investigate the prevalence of eating disorder (ED) traits among obese children and adolescents. The Swedish version of the Eating Disorder Inventory for Children, consisting of 11 subscales, was administered to 150 obese patients during an extensive investigation of causes and risk factors in obesity at the Karolinska University Hospital at Huddinge. Patients aged 17-18 years (N=24) had a mean body mass index (BMI) of 40.7, SD 5.31, and patients aged 8-16 (N=126) had a mean body mass index standard deviation score (BMI SDS) of 6.18, SD 1.69. These patients were compared with 201 girls with a diagnosed ED from the COEAT project and with a control group of schoolchildren. The comparison between obese girls and boys showed that adolescent obese girls scored higher than obese boys on Drive for Thinness, Bulimia and Body Dissatisfaction. They also scored higher on Ineffectiveness, Interoceptive Awareness and Impulse Regulation. Obese girls were close to the girls with an ED on six of the subscales. Obese boys had a lower score of Asceticism than boys in the control group. The conclusion is that psychological traits associated with disordered eating appear among obese patients, particularly among the girls. However, these patients rarely satisfy any diagnostic criteria for ED during childhood or adolescence. Since obesity treatment currently assumes rational behavior, i.e. no EDs, it is important to discover ED traits at an early age in order to adapt treatment accordingly.

Adolescent↗

PubMed1999

The use of citalopram in an integrated approach to the treatment of eating disorders: an open study.

This study investigated the efficacy and safety of citalopram in the treatment of eating disorders. Eighteen female patients gave their informed consent to enrollment in the trial: twelve with bulimia nervosa, six with anorexia nervosa according to the DSM IV criteria. They received individual systemic psychotherapy and took 20 mg/day citalopram for 8 weeks. At the beginning and end of the trial, their BMI, body fat and lean mass were checked and they completed the Eating Disorder Inventory and Binge Scale. The results showed that citalopram is effective and safe in the treatment of eating disorders: binge eating episodes and mean scores in three EDI subscales (bulimia, ineffectiveness and interoceptive awareness) significantly decreased in the bulimic patients, and mean scores in the EDI body dissatisfaction subscale significantly decreased in the anorexic patients.

Adolescent↗

PubMed2001

Evolution of symptom severity during residential treatment of females with eating disorders.

OBJECTIVES: The overall objective of this study was to measure the evolution of symptom severity in a residential programme based on a multidimensional approach to treatment that includes cognitive-behavioural, interpersonal, experiential and family therapies. The specific aims of the study were: 1) to evaluate changes in symptom severity in bulimic and anorexic patients between admission and discharge; 2) to compare the severity of these symptoms with those of non-patient college females (control group); and 3) to monitor the progression of symptom changes six months after discharge. METHODS: The evolution of symptom severity was measured by comparing the mean raw scores of the Eating Disorder Inventory (EDI original inventory, 1983 version), which was administered at the beginning and end of the residential treatment. A subgroup of patients was also administered the EDI six months after discharge. The study involved 99 females: 47 with bulimia and 52 with anorexia as diagnosed by means of a clinical interview using DSM-IV criteria. The mean raw EDI scores in the control group (FC1, female college students) were obtained from the EDI manual. The population means were compared using the t-test for paired data (Microsoft Excel, version 2000). RESULTS: The overall results for the population as a whole show that the eight subscales of the EDI improved significantly with treatment (<0.001). The subscales with the largest numerical improvements were drive for thinness, ineffectiveness and interoceptive awareness. When divided on the basis of diagnosis, the mean feelings of perfectionism score of the bulimic patients was less than that of the control female college sample; the symptoms of bulimia in the anorexic patients were similar to those found in the control group. The fact that the mean follow-up scores for a number of the ED1 subscales remained similar to those recorded at the time of discharge suggests that some of the improvements in symptoms remained for at least six months. CONCLUSIONS: The results of our study show that multidimensional residential treatment leads to statistically significant changes in the severity of the symptoms manifested by females with eating disorders.

Adolescent↗

PubMed1998

Comorbidity of obsessive compulsive disorder in patients with eating disorders.

OBJECTIVE: We investigated the prevalence of obsessive compulsive disorder (OCD) among patients with eating disorders (ED). METHOD: 66 female inpatients who met the DSM-IV criteria for anorexia nervosa (AN) or bulimia nervosa (BN) participated in the study. The Structured Clinical Interview for DSM III-R diagnoses (SCID), the Eating Disorder Inventory (EDI), the revised 90-item Symptom-Checklist (SCL-90-R), the Beck Depression Inventory (BDI), and the Toronto Alexithymia Scale (TAS-20) were carried out. RESULTS: Twelve patients (18.2%) met the DSM-III-R criteria for lifetime OCD: 7 had a current OCD and 5 had a past history of OCD. These patients had significantly higher (more pathological) mean scores on the EDI and the SCL-90-R total scales. Analyses of the EDI subscales revealed significantly higher scores for ineffectiveness, perfectionism, interoceptive awareness, and maturity fears. As expected, analyses of the SCL-90-R subscales revealed significantly higher scores for OCD. In addition, there was a trend towards higher somatization scores in patients with comorbid OCD. We could not find any significant differences in the BDI and the TAS total scores. In addition, patients with comorbid OCD showed a significantly higher lifetime prevalence of bipolar disorder, simple phobia, and somatoform disorders. DISCUSSION: Our results confirm previous reports of a strong association between ED and OCD and suggest that the prevalence of OCD may be correlated with a higher severity of the eating disorder and general psychopathological parameters.

Adolescent↗