Tamara Bushnik

Treatment of bulimia with fenfluramine and desipramine

Desipramine and fenfluramine were administered to bulimic patients in a 15-week study of double-blind, placebo-controlled, crossover design. The 22 patients in the study met DSM-III criteria for bulimia and were of normal weight. Twelve subjects were randomly allocated to the fenfluramine group, and 10 subjects received desipramine. Half the subjects in each group received the active drug in the first 6 weeks and half received placebo. There was a 3-week washout period, after which subjects were crossed over for the remaining 6 weeks. The Eating Disorder Inventory, profile of Mood States, bulimia symptom checklists, and Hopkins Symptom Checklist were administered at weeks 0, 2, 4, 6, 9, 11, 13, and 15. Subjects maintained a daily record of bingeing, vomiting, and laxative/diuretic abuse. Results indicated that both drugs had beneficial effects on bingeing and vomiting frequency, although a greater proportion of patients were identified who responded to fenfluramine than to desipramine. Fenfluramine and desipramine were also effective in reducing the psychological symptoms of bulimia, such as the urge to binge, and feelings of depression. Results suggest that direct alteration of central food intake regulatory centers can effectively control bulimia.

The substrate for brain-stimulation reward in the lateral preoptic area: I. Anatomical mapping of its boundaries

Given the putative role of the lateral preoptic area as a primary contributor of the cell bodies of origin of the descending pathway linking a subset of lateral hypothalamic and ventral tegmental area reward neurons, the distribution of self-stimulation sites in this structure was mapped in 22 animals using moveable electrodes and threshold procedures. Ninety-seven electrode sites were evaluated with placements ranging from just rostral to the midline convergence of the anterior commissure back to the transition zone between the lateral preoptic and lateral hypothalamic areas; of these, roughly 2/3 supported self-stimulation which was widely observed throughout the lateral preoptic area and medial forebrain bundle. In general, self-stimulation thresholds obtained from lateral sites were most stable, and progressively so approaching more caudal regions. Examination of the slopes of the period/current trade-off functions revealed a tendency for higher values in lateral and caudal sites; in contrast, dorsoventral excursions did not influence these estimates. Taken together, these data provide support for the notion that the substrate for brain-stimulation reward in the lateral preoptic area has a relatively homogeneous distribution that is more diffusely organized than that found in reward sites activated further caudally in the medial forebrain bundle.

Physiological and psychological responses to a glucose challenge in bulimia

Twenty females meeting DSM-III criteria for bulimia, and 12 age- and sex-matched controls underwent a 60-min intravenous glucose tolerance test. Blood samples were taken at −10, 0, 5, 10, 20, 30, 45, and 60 min after the glucose injection. At these times, subjects completed a mood rating scale [Profile of Mood States (POMS)] and a subjective self-report questionnaire addressing both food cravings and thirst, as well as the urge to binge and subjective control over food intake. Blood levels of tryptophan, tyrosine, valine, leucine, phenylalanine, and isoleucine were measured at 0 and 60 min after the injection. Although equivalent at baseline, the blood glucose levels of bulimics at 5 min and insulin/glucagon ratio at 20, 30, and 45 min following injection were reduced in comparison to controls. Blood valine levels were also lower among the bulimic group. There were no differences between the bulimics and normal controls at baseline on subjective self-report measures of urge to binge, control over food intake, carbohydrate (CHO) craving or fatigue. following the glucose injection, however, the observed physiological differences between the two groups were accompanied by increased subjective cravings for sweets and fruits, an enhanced urge to binge, and less subjective control over food intake for bulimics as compared with controls. The bulimics also reported increased fatigue in response to glucose, whereas controls reported feeling less fatigued. The results suggest that abnormal physiological responses to blood glucose are accompanied by alterations in both food cravings and mood, which may promote binging among bulimic patients.

The substrate for brain-stimulation reward in the lateral preoptic area. II. Connections to the ventral tegmental area.

This experiment investigated the existence of a direct anatomical connection between lateral preoptic and ventral tegmental areas that mediate brain stimulation reward using the behavioral adaptation of the collision test. This test is a double-pulse, two-electrode technique based on the axonal conduction failure that occurs when two separate sites in the same axon bundle are concurrently stimulated. This anatomical arrangement is inferred from the shape of the function relating the effectiveness of double-pulse stimulation to the interval between pulses. In this study, nine rats with a total of 44 pairs of sites were examined. In two pairs only was there a profile suggestive of an axonal collision effect, while the double-pulse effectiveness curve consistent with the properties of transynaptic collision was apparent for a single pair of sites; the remaining 93% were associated with relatively flat effectiveness curves. While electrode misalignment could be responsible for these results, there was adequate sampling to suggest that the preponderance of first stage signals that give rise to the rewarding effects mediated by the lateral preoptic and ventral tegmental areas do not travel along the same fiber bundle. However, stimulation applied to both sites concurrently produces a summation that is roughly 40% greater than stimulation at either site alone, suggesting reasonable integration of the reward signals generated by lateral preoptic and ventral tegmental area stimulation.

A double-blind placebo-controlled glucose challenge in bulimia nervosa: Psychological effects☆

Nineteen bulimic women and 22 age-matched controls were randomly assigned to receive 25 g of glucose or a placebo injection under double-blind conditions. Blood samples of glucose, insulin, and glucagon, and psychometric assessments of mood and food cravings were obtained 10 min before, and 0, 5, 10, 20, 30, 45, and 60 min after injection. Blood levels of the large neutral amino acids (LNAAs) tryptophan, tyrosine, leucine, valine, phenylalanine, and leucine were determined at 10 min before and 60 min after the injection. Bulimic subjects were found to report more symptoms of distressed mood throughout the entire monitoring period than controls. Five minutes following glucose ingestion the self-reports of depression, fatigue, anxiety, and bewilderment rose to a level among the bulimic subjects that was above that at baseline, and was higher than that of bulimia nervosa (BN) subjects receiving placebo. No comparable change in mood was observed among controls. Blood glucose levels were correlated with mood in the bulimic group, but not in controls. In addition, the glucose injection induced a heightened urge to binge in the bulimic group (compared to placebo at 10 and 60 min), whereas reducing food cravings (for sweets) in the controls (at 5 min). When collapsed across time and injection condition, the blood glucose level of bulimics was lower than that of controls. There were no differences in insulin response between the groups. The bulimic group was found to have lower baseline levels of blood tryptophan, whereas no differences in the tryptophan/LNAA ratio were observed either at baseline or following glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Bulimia and diabetes: Distinct psychosocial profiles

A higher incidence of bulimia in diabetic populations than in the normal population has been reported. This study examined whether psychosocial similarities between bulimics and diabetics might exist, posing a psychological risk factor for bulimia among diabetics. Diabetics (n = 79), bulimics (n = 19), and controls (n = 19) were administered tests of eating attitudes, psychiatric symptomatology, and family environment. Few significant psychological Similarities were found between the bulimic and diabetic groups. The diabetic and control groups exhibited less psychopathology than the bulimic group on almost all indices. Although both diabetics and bulimics were found to be more perfectionistic than controls, this alone is insufficient evidence of a psychological risk factor for bulimia in the diabetic population studied.

Diazepam facilitates stimulation-induced feeding in rats

The effect of diazepam on the trade-off function between current and frequency for stimulation-induced feeding was evaluated in five rats with electrodes implanted in medial forebrain bundle structures. Three of the five exhibited stimulation-induced feeding (SIF) in vehicle tests, while in the remaining two attention to food was interspersed with periods of high activity. In all cases diazepam facilitated stimulation-induced feeding; the expression of stimulation-induced feeding was observed at a dose of 2.5 mg/kg and 5.0 mg/kg, where tested, and frequency threshold shifts ranged from 10% to 25%. The degree of facilitation was consistent across currents in two of the four pairs of trade-off functions examined. The results suggest that diazepam can facilitate stimulation-induced feeding and its expression in feeding sites with a competing arousal component.

Control of Motor Seizures by Brotizolam With Maintenance of Stable Refractory Periods for Self-Stimulation

In recent years, we have been pursuing our mapping investigations of the substrate for brain-stimulation reward in regions of the anterior hypothalamic and lateral preoptic areas. However, one problem is that stimulation of these sites often generates overt seizures so that their suppression via a pharmacological means would be very useful. The sedative-hypnotic benzodiazepine, brotizolam, is reportedly a long-lasting anticonvulsant. Hence, its effects on motor seizures elicited from stimulation of the lateral preoptic area were evaluated in the first experiment. Both tested doses (5.0 and 7.5 mg/kg) of the drug were shown to significantly decrease the number, and marginally, the severity of stimulation-induced seizures; furthermore, this effect was relatively long lasting, up to about 3 h. The higher dose of brotizolam did not alter the single-pulse thresholds for self-stimulation, a requirement for evaluations of poststimulation excitability, the purpose of the second experiment. Here, our interest was in documenting whether the membrane properties of the stimulated neurons, as assessed by refractory periods, were altered by brotizolam. No differences in the time course of recovery were observed; refractoriness began between 0.4 and 0.8 ms, and reached 50% recovery by 2.0 ms, which is consistent with the pattern of poststimulation excitability typically measured at these sites. Thus, in addition to its long-lasting suppression of motor seizures in rats, brotizolam does not alter the time course of recovery from refractoriness of the neurons that mediate brain-stimulation reward in the lateral preoptic area.