The neuroendocrinology of anhedonia

Abstract

One of the more fascinating developments in neuroscience is the recognition of endocrine influences on brain regions unrelated to reproductive and basic homeostatic functions. It is now clear that hormones impact both normal function and dysfunction, including the experience of pleasure and the anhedonia accompanying a number of psychiatric disorders, most notably depression. Brain regions contributing to these functions are rich in receptors for the peptides and steroids of the hypothalamic - pituitary - gonadal (HPG) and hypothalamic - pituitary - adrenal (HPA) axes. Indeed, the brain has evolved new functions for ancient hormones. Examples include the brain adaptive uses of steroid precursors and metabolites for non-reproductive functions and the brain co-opting or “hijacking” peptides of the two axes to serve as neuromodulators and neurotransmitters. The result is that HPA and HPG hormones and their interactions have profound influences on opioids and monoamines, especially dopamine and serotonin. These are the same neurotransmitter pathways underlying activation of the brain reward pathway stretching from midbrain to the prefrontal cortex. Our ultimate goal is to fulfill the promise of the title, an evaluation of neuroendocrine - anhedonia relations. This requires, first, an overview of the endocrine system, and their steroids and peptides. There, we also provide a brief review of the interaction of the HPA and HPG axes in depression. Before embarking on an evaluation of hormones and anhedonia, we will examine normal neuroendocrine influences on pleasure from natural experiences such as food and sex but also from psychoactive drugs. Logic suggests examining data on pleasure before addressing loss of pleasure. The emphasis throughout will be on animal models with a liberal sprinkling of human findings, mostly psychiatric patients. This journey will take us through endocrine basics (Sect. 10.1), and the influence of hormones on brain systems underlying the experience of pleasure (Sect. 10.2). In Sect. 10.3, the modest literature on the neuroendocrinology of anhedonia in depression will be reviewed. Finally, future research and directions (Sect. 10.4) will provide ideas on filling in the gaps in our understanding of endocrine - anhedonia relations.