Dean D. Krahn

CRF antagonist partially reverses CRF- and stress-induced effects on feeding

Exogenous corticotropin releasing factor (CRF) causes centrally mediated behavioral changes including decreased feeding and increased grooming. These behavioral changes are also seen in response to some stressors. However, the role of endogenous CRF in the behavioral response to stressors has not been investigated fully. We report below our findings on the behavioral effects of alpha-helical CRF (9-41), a recently discovered competitive antagonist of CRF-induced ACTH release. Alpha-helical CRF (9-41) partially reversed the decrement in feeding induced by CRF. Furthermore, the reduction in food intake due to restraint stress was partially reversed by alpha-helical CRF (9-41). These results indicate that changes in endogenous CRF release induced by the restraint stressor may play a role in stress-induced anorexia.

Effects of calcitonin gene-related peptide on food intake

Recently, calcitonin gene-related peptide (CGRP), a product of alternative processing of RNA transcripts from the calcitonin gene, has been characterized. CGRP is present in a number of areas of the brain involved in modulating ingestive behaviors. We tested the effect of centrally administered CGRP on ingestive behaviors. ICV CGRP over a dose range of 1 to 10 micrograms suppressed food intake in 24 hr deprived rats and 20 and 10 micrograms decreased spontaneous nocturnal food intake. CGRP was less effective than calcitonin at suppressing food intake. Peripheral CGRP was less effective than centrally administered CGRP. Behaviorally, CGRP treated animals rested more, groomed less and ate less. Central CGRP (10 micrograms) did not alter circulating glucose levels. These results suggest that CGRP in high doses may be centrally active in regulating consummatory behaviors.

Peptides as central regulators of feeding

During the past decade there has been an increased awareness of the role peptides play as neuromodulators. In this article we review the available data on peptides as central regulators of food ingestion. We stress the possible problems of non-specific effects. We stress that whereas many peptides decrease feeding after central injection, only two families of peptides have been shown to increase feeding after central injection. These are the opioid family and the pancreatic polypeptide-neuropeptide Y family. The putative role of corticotropin releasing factor as the mediator of norepinephrine and serotonin effects on feeding is discussed.

Peptides and feeding

This report reviews the hypothesis that peptides play a role in appetite modulation, stressing that the available evidence is predominantly pharmacological and thus caution needs to be taken in assigning physiological significance at this time. Two peptide systems have been postulated--a peripheral satiety system, typified by the gastrointestinal hormone cholecystokinin and a central feeding system driven by the opioid peptides and neuropeptide Y. This review also discusses the putative role of peptides in the anorexia of aging, drinking elicited by feeding and as mediators of the autonomic effects seen in association with ventromedial hypothalamic lesions.

Psychoneuroendocrine effects of methadone maintenance

A variety of neuroendocrine and psychiatric dysfunctions have been demonstrated in humans maintained on opiates, but both have not previously been examined in the same population. We performed a series of neuroendocrine challenge tests in men participating in a methadone maintenance clinic and in normal controls. Psychiatric diagnoses were made with DSM-III Criteria, using the Diagnostic Interview Schedule, and subjects also completed the Symptom Checklist. Our results in the methadone group suggest (a) near-maximal stimulation of prolactin secretion, with a blunted prolactin response to insulin hypoglycemia, (b) mild suppression of cortisol levels, but an exaggerated cortisol response to stimulation, (c) a delayed and inhibited insulin response to food ingestion with resulting mild hyperglycemia, (d) low body weight, but elevated calorie ingestion, and (e) inability to concentrate urine when dehydrated, which was partially corrected by administration of arginine vasopressin. Phobic disorder was associated with a lower prolactin response to both inhibitory and stimulatory challenges. Depression did not appear to be related to the increased cortisol response to stimulation. These results suggest several potentially fruitful areas for future investigation, including the prolactin system and anxiety disorders, nutrient ingestion and metabolism, and posterior pituitary function.

Effect of morphine and nalmefene on energy balance in diabetic and non-diabetic rats

Male rats made diabetic by intravenous injection of streptozotocin were used to evaluate the effect of the diabetic state on morphine- and nalmefene-induced changes in food intake and body weight. Morphine increased 4 hour food intake in non-diabetic rats after an initial injection, but increased intake in diabetic rats only after repeated injections. Unlike short term measurements, morphine decreased food intake when measured over 24 or more hours in both groups. Chronic injection of morphine decreased body weight only in non-diabetic rats. Feed efficiency data suggest that morphine had a more potent effect on energy balance in the non-diabetic rats. The opioid antagonist, nalmefene, did not alter body weight in either group and only altered food intake in the diabetic animals. These data are in concert with other reports indicating that the diabetic state renders animals less responsive to the effects of morphine on nociception and smooth muscle contraction.

Dieting and Alcohol Use in Women

The connection between dieting, which involves the restriction of caloric intake and especially the avoidance of the intake of “empty” calories, and alcohol consumption, which involves the intake of calories that are not nutritionally vital, is not intuitively obvious to many. Therefore, the reader of this chapter may benefit from a recounting of the way in which we came to study this problem. We recognize that this may be viewed as a rather egocentric approach by some, but in our experience with talking about this area of interest with colleagues, we have found that this type of review tends to be an understandable approach to this topic. The comorbidity of eating disorders and substance abuse have also been reviewed extensively elsewhere,1,2and more emphasis regarding family history and clinical implications are available in these sources.