Hypothalamus anxiety

CRH (Corticotropin releasing hormone) is expressed in the nucleus paraventricularis of the hypothalamus and drives the stress hormone system by activating synthesis and release of corticotropin at the pituitary and in turn corticosteroid from the adrenal cortex. CRH is also expressed at many other brain locations not involved in neuroendocrine regulation, e.g. the prefrontal cortex and the amygdala. Preclinical studies have shown that CRH also coordinates the behavioral adaptation to stress (e.g. anxiety, loss of appetite, decreased sleepiness, autonomic changes, loss of libido). 

Neuropeptide S (NPS) is a recently discovered bioactive peptide that has emerged as a new signaling molecule in the complex circuitry that modulates sleep-wakefulness and anxiety-like behavior. The peptide precursor is expressed most prominently in a novel nucleus located in the perilocus coeruleus, a brain structure with well-defined functions in arousal, stress, and anxiety. NPS was also found to induce anxiolytic-like behavior in a battery of four different tests of innate responses to stress. Infusion of NPS potently increases wakefulness and suppresses non-REM (NREM) and REM sleep (Xu et al, 2004). NPS binds to a G-protein-coupled receptor, the NPS receptor, with nanomolar affinity activation of the receptor mobilizes intracellular calcium. The NPS receptor is expressed throughout the brain, particularly in regions relevant to the modulation of sleep and waking, in the tuberomammillary region, lateral hypothalamus, and medial thalamic nuclei. 

The amygdala is perhaps the best-studied, and most strongly implicated, brain structure in anxiety and fear. Electrical stimulation of the amygdala produces fear-like behavioral and physiological responses in animals, and increases the suggestive experience of fear in human subjects. Additionally, amygdala stimulation leads to corticosterone secretion and HPA-axis activation in animals, probably via outputs to the hypothalamus and the bed nucleus of the stria terminalis. It has been suggested... 

CRH and its receptors have generated increasing interest as a target for medications. In addition to the pituitary, CRH receptors have been localized to the cortex, the nuclei of the amygdala, the LC, and regions of the hypothalamus. It has also been reported that CRH increases LC activity, and that local injection of CRH into the LC increases behavioral responses consistent with increased anxiety [105]. Furthermore, CRH antagonists have been repeatedly shown to have anxiolytic effects in animal models. 

During the expression of fear-related behaviors, the LA engages the central nucleus of the amygdala (CEA), which, as the principal output nucleus, projects to areas of the hypothalamus and brain stem that mediate the autonomic, endocrine, and behavioral responses associated with fear and anxiety (Schafe et al. 2001). The molecular and cellular mechanisms that underlie synaptic plasticity in amygdala-dependent learned fear is an area of very active investigation (Shumyatsky et al. 2002). Long-term potentiation (LTP) in the LA appears to be a critical mechanism for storing memories of the CS-US associa-... 

Sensitization Dopaminergic, noradrenergic NMDA receptors Nucleus accumbens, amygdala, striatum, hypothalamus May explain the adverse effects of early life trauma on subsequent responses to stressful like events. May play a role in the chronic course of many anxiety disorders and, in some cases, the worsening of the illness over time Suggests the efficacy of treatment may vary according to the state of evolution of the disease process. Emphasizes the importance of early treatment intervention... 

The nonapeptide vasopressin (AVP) is synthesized in the paraventricular nucleus of the hypothalamus (PVN) and the nucleus supraopticus. Besides its role in fluid regulation, AVP is also a key modulator of the HPA system, where it potentiates the effects of CRH on adrenocorticotropic hormone (ACTH) release. Extrahypothalamic AVP-containing neurons are localized in the medial amygdala and the bed nucleus of the stria terminalis. AVP applied intracere-broventricularly or to the lateral septum has been shown to affect cognition, social behavior, and anxiety-like behavior in rodents (Insel et al. 2001). 

Patchev VK, Shoaib M, Holsboer F, et al The neurosteroid tetrahydroprogesterone counteracts corticotropin-releasing hormone-induced anxiety and alters the release and gene expression of corticotropin-releasing hormone in the rat hypothalamus. Neuroscience 62 265-271, 1994... 

Serotonin (also known as 5-hydroxytryptamine) is released by cells originating in the midline of the pons and brainstem and is projected to many different areas, including the dorsal horns of the spinal cord and the hypothalamus. Serotonin is considered to be a strong inhibitor in most areas of the CNS and is believed to be important in mediating the inhibition of painful stimuli. It is also involved in controlling many aspects of mood and behavior, and problems with serotonergic activity have been implicated in several psychiatric disorders, including depression and anxiety.12,17 The roles of serotonin and the other monoamines in psychiatric disorders are discussed in Chapters 6-8. 

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