TY - CHAP M1 - Book, Section TI - Mood and Emotion A1 - Nestler, Eric J. A1 - Kenny, Paul J. A1 - Russo, Scott J. A1 - Schaefer, Anne Y1 - 2020 N1 - T2 - Nestler, Hyman & Malenka’s Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, 4e AB - KEY CONCEPTSEmotions activate physiologic, cognitive, and behavioral outputs that facilitate adaptive responses to salient external and internal stimuli.A crucial emotion, important in several mental disorders, is fear. The neural circuitry of fear is well understood because fear can be reliably elicited in animal models, and because its effects can readily be measured.Information about threatening stimuli is transmitted from the thalamus and cerebral cortex to the amygdala where it is processed; neurons carrying fear–related information then project to diverse downstream sites in the brain responsible for adaptive responses.Anxiety, a state characterized by arousal, vigilance, physiologic preparedness, and, in humans, negative subjective states, shares some critical circuits with fear.Because of the evolutionary conservation of key neural circuits, animal research on fear has relevance to humans. Several anxiety disorders may involve abnormal regulation of amygdala–based fear circuitry.Mood disorders are divided into “unipolar disorders,” which are characterized by depression only, and bipolar disorder, which is diagnosed if the person has ever had an episode of mania.Mood disorders are influenced by both genes and environment, with genes playing a greater role in bipolar than in unipolar disorders.Animal models to study mood regulation and mood disorders are far from perfect. However, in concert with human experiments involving functional neuroimaging, studies of postmortem brain tissue, and clinical trials of deep brain stimulation, a picture of mood–regulating circuits is emerging.A subset of individuals with major depression exhibit excessive activation of the hypothalamic–pituitary–adrenal axis, one of many stress–responsive systems in the body; thus, certain cases of depression share some physiologic mechanisms with chronic stress.Most of the effective pharmacologic treatments for depression act on protein targets within monoamine synapses, generally enhancing neurotransmission by norepinephrine, serotonin, or both. A similar role for dopamine is postulated but unproven.Although the initial molecular targets of antidepressants are well characterized, their actual mechanism of action is not understood. The several–week latency of onset of therapeutic effects suggests that slowly developing adaptive responses to initial enhancement of monoamine neurotransmission are required for efficacy.Current research aimed at developing more effective antidepressants with novel mechanisms of action is focused on several forebrain regions and the actions of numerous neurotransmitter systems, neurotrophic factors, cytokines, intracellular signaling pathways, and transcriptional regulatory mechanisms.The discovery of ketamine, an NMDA glutamate receptor antagonist (among other actions), as a rapidly acting antidepressant, and brexanolone (allopregnanolone) as a specific treatment for postpartum depression, represent the first mechanistically distinct (ie, nonmonoamine–acting), US FDA–approved antidepressants in nearly a half century, opening up new avenues in depression and antidepressant research. SN - PB - McGraw-Hill CY - New York, NY Y2 - 2024/03/28 UR - neurology.mhmedical.com/content.aspx?aid=1174974662 ER -