Neurochemical mechanisms involved in the anticipation, ingestion and termination of a meal: Focus on corticotropin-releasing hormone and bombesin-like peptides

Abstract

The apparently simple decision to initiate or terminate a meal is extremely complex. However, the need to determine the physiological and psychological mechanisms regulating these processes has taken on an air of urgency due to escalating levels of eating disorders in our society. Ingestive patterns are influenced by a number of factors, including signaling circuits utilizing peptides, such as corticotropin-releasing hormone (CRH) and bombesin-like peptides (BN-LPs). As some of the peptidergic systems under study have also been implicated in the mediation of the stress response, some peptidergic linkages between 'stress' and 'satiety' responses are also explored. The overall objective of this thesis was to examine the pattern of utilization or release of BN-LPs and CRH at specific brain loci during (1) various phases of food ingestion, (2) the presentation of anticipatory cues paired with an appetitive event, and (3) exposure to stressors. Using in vivo microdialysis, we demonstrated that both CRH and BN-LPs are released from the central nucleus of the amygdala in response to both restraint stressor exposure and spontaneous food ingestion, an effect that was mirrored at the anterior pituitary. Furthermore, we demonstrated that CRH and BN-LPs were released at the medial prefrontal cortex in response to the "anticipation" of a palatable snack. These results raised the intriguing possibility that some aspects of both the feeding behavior and the organism's response to stressor exposure are being subserved by a common neurochemical mechanism(s). As such, it would be expected that variables that affect an organism's stress response would also have an impact on feeding behavior and related neurochemical processes. In fact we found that early life experience, gender and genetics variables (that appear to impact the stress response) also impact on the animal's neurochemical response(s) to ingestion as well as their propensity to consume a palatable snack. These experiments extend our current knowledge of the mechanism(s) underlying the control of food intake and support our contention that these systems may also serve to draw attention to events or cues of biological salience. Finally, these results also provide new insights into the potential mechanism(s) underlying various stress and eating dysfunctions, including anorexia nervosa, anorexia associated with AIDS, cancer, sickness or stress, bulimia nervosa, obesity and depression.