Introduction

The laboratory of Catherine Rivier is part of The Clayton Foundation Laboratories for Peptide Biology, a department that houses six faculty members whose research spans neural development and function, structure and function of peptide hormones, role of neuroendocrine genes in neural and endocrine signaling, and neurobiology of ion channels. By bringing together scientists with varied interests, our department allows us to benefit from one another's scientific expertise with the ultimate goal of elucidating the mechanisms controlling neuroendocrine systems, and thus contributing to the optimization of human health.

Our research focuses on hormones, the chemical messengers that mediate interactions between the brain, the immune system, and the neuroendocrine systems. Specifically, we investigate how the brain perceives the occurrence of homeostatic challenges ("stressors"), and how it responds to them. This work includes the identification of the brain regions that are activated by specific stressors (including exposure to drugs such as alcohol), the characterization of the neuromediators (peptides, amines, gasses, etc.) whose synthesis and release is stimulated by these stressors, and the type of neuroendocrine responses that are elicited. For example, we showed that production of the unstable gas nitric oxide is increased in the hypothalamus of rodents exposed to various stressors, and that this increase participates in the activation of the hypothalamic-pituitary-adrenal (HPA) axis. With regard to alcohol, we showed that rodents exposed to this drug during embryonic development show enhanced levels of the hypothalamic peptide corticotropin-releasing factor, as well as elevated adrenal responses to stressors, when they reach adulthood. If comparable changes take place in humans, they could participate in several of the pathologies that accompany conditions related to fetal alcohol syndrome, including anxiety, attention deficit and increased occurrence of infections. With regard to postnatal alcohol abuse, we have started to use models of dependence to investigate the role played by the HPA axis in relapse. Stress is thought to play a role in the ability of addicted individuals to maintain abstinence. Thus, a better understanding of the function of the HPA axis during the development of alcohol dependence, and of how the activity of this axis differs between dependent and non-dependent animals, will be helpful in the development of novel therapies. Recently, we also developed a model of prenatal stress in rodents, which causes permanent anxiety in adult offspring. This will allow us to investigate some of the mechanisms leading to altered neuroendocrine functions during anxiety and depression, and specifically to address the role of the HPA axis in these mood disorders. In view of the recent discovery that changes in HPA axis characterize many types of anxiety and depression, a better understanding of the neural circuitry activity of this axis in these pathologies may provide leads into novel therapies. Finally, one of our most recent discoveries is the existence of a neural pathway through which the brain controls the activity of the testes that is independent of the pituitary. This discovery, which is likely to change the way we conceptualize the control of male reproductive functions, may help us understand some puzzling cases of low testosterone secretion due to stressors or diseases. It may also help develop novel approaches for the treatment of diseases characterized by low androgen levels.