Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence from many different laboratories using a variety of experimental techniques and animal species indicates that the amygdala plays a crucial role in conditioned fear and anxiety, as well as attention. Many amygdaloid projection areas are critically involved in specific signs used to measure fear and anxiety. Electrical stimulation of the amygdala elicits a pattern of behaviors that mimic natural or conditioned fear. Lesions of the amygdala block innate or conditioned fear, as well as various measures of attention, and local infusions of drugs into the amygdala have anxiolytic effects in several behavioral tests. N-methyl-D-aspartate (NMDA) receptors in the amygdala may be important in the acquisition of conditioned fear, whereas non-NMDA receptors are important for the expression of conditioned fear. The peptide corticotropin-releasing hormone appears to be especially important in fear or anxiety and may act within the amygdala to orchestrate parts of the fear reaction.
 ...
PMID:Neurobiology of fear responses: the role of the amygdala. 927 41

We examined the role of the hippocampal cholinergic system, which is known to mediate processes related to fear and anxiety, in the regulation of stress-induced hypothalamic-pituitary-adrenal (HPA) activity. Bilateral intra-hippocampal injections (30 microg per side) of the muscarinic antagonist Scopolamine augmented adrenocorticotropin and corticosterone responses to restraint without altering basal HPA activity compared to vehicle-treated animals. These results suggest that the hippocampal cholinergic system regulates stress-induced HPA activity and may serve to coordinate behavioral and neuroendocrine responses to stress.
 ...
PMID:Hippocampal cholinergic blockade enhances hypothalamic-pituitary-adrenal responses to stress. 935 9

The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased alpha2 adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to the forebrain structures. Considering the importance of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression of behavioral responses to stress, these findings suggest that maternal care during infancy serves to "program" behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.
 ...
PMID:Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. 956 Feb 76

There is wide agreement that corticotropin-releasing hormone (CRH) systems within the brain are activated by stressful stimuli. There is also mounting evidence for the role of bombesin (BN)-like peptides in the mediation of the stress response. To date, however, the extent to which other stimuli increase the activity of these peptidergic systems has received little attention. In the present investigation we validated and used in vivo microdialysis sampling followed by ex vivo radioimmunoassays to monitor the release of CRH and BN-like peptides during appetitive (food intake) and stressful (restraint) events. It is demonstrated for the first time that the in vivo release of CRH and BN-like peptides at the central nucleus of the amygdala was markedly increased by both stressor exposure and food ingestion. In fact, the meal-elicited rise of CRH release was as great as that associated with 20 min of restraint stress. Paralleling these findings, circulating ACTH and corticosterone levels were also increased in response to both food intake and restraint. Contrary to the current views, these results indicate that either food ingestion is interpreted as a "stressful" event by certain neural circuits involving the central amygdala or that the CRH- and BN-related peptidergic systems may serve a much broader role than previously envisioned. Rather than evoking feelings of fear and anxiety, these systems may serve to draw attention to events or cues of biological significance, such as those associated with food availability as well as those posing a threat to survival.
 ...
PMID:Aversive and appetitive events evoke the release of corticotropin-releasing hormone and bombesin-like peptides at the central nucleus of the amygdala. 961 49

Evidence supports the idea of two distinct corticotropin-releasing hormone (CRH) systems in the brain: one which is constrained by glucocorticoids and the other which is not. It is this latter system that includes two primary sites (central nucleus of the amygdala and the lateral bed nucleus of the stria terminalis) in which the regulation of CRH gene expression can be disassociated from that of the paraventricular nucleus of the hypothalamus. It is this other system that we think is linked to fear and anxiety and to clinical syndromes (excessively shy fearful children, melancholic depression, post-traumatic stress disorder and self-administration of psychotropic drugs). The excess glucocorticoids and CRH, and the state of anticipatory anxiety, contribute to allostatic load, a new term that refers to the wear and tear on the body and brain arising from attempts to adapt to adversity.
 ...
PMID:Induction of corticotropin-releasing hormone gene expression by glucocorticoids: implication for understanding the states of fear and anxiety and allostatic load. 969 28

Although there is a close correspondence between fear and anxiety, and the study of fear in animals has been extremely valuable for understanding brain systems that are important for anxiety, it is equally clear that a richer animal model of human anxiety disorders would include measures of both stimulus-specific fear and something less stimulus specific, more akin to anxiety. Studies in patients with posttraumatic stress syndrome indicate these individuals seem to show normal fear reactions but abnormal anxiety measured with the acoustic startle reflex. Studies in rats, also using the startle reflex, indicate that highly processed explicit cue information (lights, tones, touch) activates the central nucleus of the amygdala, which in turn activates hypothalamic and brain stem target areas involved in specific signs of fear. Somewhat less explicit information, such as that produced by exposure to a threating environment for several minutes or by intraventricular administration of the peptide corticotropin-releasing hormone may activate a brain area closely related to the amygdala, called the bed nucleus of the stria terminalis, which in turn activates hypothalamic and brain stem target areas involved in specific signs of fear or anxiety. Because the nature of this information may be less specific than that produced by an explicit cue, and of much longer duration, activation of the bed nucleus of the stria terminalis may be more akin to anxiety than to fear.
 ...
PMID:Are different parts of the extended amygdala involved in fear versus anxiety? 986 67

The main biological role of angiotensin II type 2 receptor (AT2) has not been established. We made use of targeted disruption of the mouse AT2 gene to examine the role of the AT2 receptor in the central nervous system (CNS). AT2-deficient mice displayed anxiety-like behavior compared with wild-type mice. However, AT2-deficient mice showed no depressant-like activity and no change in hexobarbital-induced sleeping time as compared with findings in wild-type mice. Both noradrenergic and corticotropin-releasing factor (CRF) neuronal systems appear to be involved in this anxiety-like behavior. Diazepam, captopril (angiotensin I converting enzyme inhibitor), prazosin (alpha1 antagonist) reversed the anxiety-like behavior in these AT2-deficient mice, whereas yohimbine (alpha2 antagonist), phenylephrine (alpha1 agonist), clonidine (alpha2 agonist), isoproterenol (beta1/beta2 agonist), propranolol (beta1/beta2 antagonist) and alpha-helical CRF9-41 (CRF receptor antagonist) has no apparent effects on anxiety-like behavior in AT2-deficient mice. In addition, concentrations of plasma adrenocorticotropic hormone (ACTH) and corticosterone in AT2-deficient mice did not differ from these in wild-type mice, hence, there are probably no endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis (HPA). The amygdala appears to play an important role in many of the responses to fear and anxiety. The number of [3H]prazosin but not [125I]CRF binding sites in the amygdala was significantly reduced in AT2-deficient mice. These findings indicate that the noradrenergic system is involved in mediating the anxiety-like behavior in AT2-deficient mice.
 ...
PMID:Anxiety-like behavior in mice lacking the angiotensin II type-2 receptor. 1006 99

Although there is a close correspondence between fear and anxiety, and the study of fear in animals has been extremely valuable for understanding the neural basis of anxiety, it is also clear that a richer animal model of human anxiety disorders would include measures of both stimulus-specific fear and something less stimulus specific, more akin to anxiety. Patients with posttraumatic stress syndrome seem to show normal fear reactions but abnormal anxiety measured with the acoustic startle reflex. Studies in rats, also using the startle reflex, indicate that highly processed explicit cue information (lights, tones) activates the central nucleus of the amygdala, which projects to and modulates the acoustic startle pathway in the brain stem. Less explicit information, such as that produced by exposure to a threatening environment or by intraventricular administration of corticotropin-releasing hormone, may activate another part of the extended amygdala, the bed nucleus of the stria terminalis, which also projects to the startle pathway. Because this information may be less specific and of long duration, activation of the bed nucleus of the stria terminalis may mediate anxiety, whereas activation of the central nucleus of the amygdala may mediate stimulus-specific fear.
 ...
PMID:The extended amygdala: are the central nucleus of the amygdala and the bed nucleus of the stria terminalis differentially involved in fear versus anxiety? 1041 55

Throughout life organisms are challenged with various physiological and psychological stressors, and the ability to handle these stressors can have profound effects on the overall health of the organism. In mammals, the effects of stressors on the aging process and age-related diseases are complex, involving the nervous, endocrine and immune systems. Certain types of mild stress, such as caloric restriction, may extend lifespan and reduce the risk of diseases, whereas some types of psychosocial stress are clearly detrimental. We now have a basic understanding of the brain regions involved in stress responses, their neuroanatomical connections with neuroendocrine pathways, and the neuropeptides and hormones involved in controlling responses of different organ systems to stress. Not surprisingly, brain regions involved in learning and memory and emotion play prominent roles in stress responses, and monoaminergic and glutamatergic synapses play particularly important roles in transducing stressful sensory inputs into neuroendocrine responses. Among the neuropeptides involved in stress responses, corticotropin-releasing hormone appears to be a pivotal regulator of fear and anxiety responses. This neuropeptide is responsible for activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is critical for mobilizing energy reserves and immune responses, and improper regulation of the HPA axis mediates many of the adverse effects of chronic physical and psychosocial stress. In the brain, for instance, stress may contribute to disease processes by causing imbalances in cellular energy metabolism and ion homeostasis, and by inhibiting neuroprotective signaling pathways. There is considerable evidence that normal aging impacts upon neuroendocrine stress responses, and studies of the molecular and cellular mechanisms underlying the pathogenic actions of mutations that cause age-related neurological disorders, such as Alzheimer's disease, are revealing novel insight into the involvement of perturbed neuroendocrine stress responses in these disorders.
 ...
PMID:Impact of aging on stress-responsive neuroendocrine systems. 1134 61

The bed nucleus of the stria terminalis (BNST) has a high density of corticotropin-releasing hormone (CRH)-containing neurons that are significantly innervated by noradrenergic and dopaminergic nerve terminals. This limbic structure is involved in the extrahypothalamic response to stress. The purpose of the present work is to study whether the absence of glucocorticoids, induced by a long-term adrenalectomy, regulates CRH gene expression and noradrenaline and dopamine extracellular levels in the rat BNST. The results showed that adrenalectomy decreases CRH mRNA in the dorsal lateral BNST but not in the ventral lateral BNST. Adrenalectomy also decreases CRH-like immunoreactivity both in BNST subnuclei and in the central nucleus of the amygdala. In addition, adrenalectomy significantly increases noradrenaline and dopamine extracellular levels in the lateral BNST. The present results suggest that adrenalectomy regulates CRH gene expression and noradrenaline and dopamine extracellular levels in the BNST in an opposite way. Thus, the present study adds novel evidence further supporting that the BNST and the central nucleus of the amygdala form part of an adrenal steroid-sensitive extrahypothalamic circuit that has been involved in fear and anxiety responses and in clinical syndromes such as melancholic depression, posttraumatic stress disorders, and addiction.
 ...
PMID:Adrenalectomy decreases corticotropin-releasing hormone gene expression and increases noradrenaline and dopamine extracellular levels in the rat lateral bed nucleus of the stria terminalis. 1593 75


1 2 Next >>