Noradrenergic mechanisms in stress and anxiety: I. preclinical studies

Abstract

There is considerable preclinical evidence for a relationship between noradrenergic brain systems and behaviors associated with stress and anxiety. The majority of noradrenergic neurons are located in the locus coeruleus (pons), with projections throughout the cerebral cortex and multiple subcortical areas, including hippocampus, amygdala, thalamus, and hypothalamus. This neuroanatomical formation of the noradrenergic system makes it well suited to rapidly and globally modulate brain function in response to changes in the environment, as occurs during the presentation of stressors. Stress exposure is associated with an increase in firing of the locus coeruleus and with associated increased release and turnover of norepinephrine in brain regions which receive noradrenergic innervation. Increased firing of the locus coeruleus is also associated with behavioral manifestations of fear, such as arched back and piloerection in the cat. Exposure to chronic stress results in long‐term alterations in locus coeruleus firing and norepinephrine release in target brain regions of the locus coeruleus. Norepinephrine is also involved in neural mechanisms such as sensitization and fear conditioning, which are associated with stress. These findings are relevant to an understanding of psychiatric disorders, such as panic disorder and post‐traumatic stress disorder (PTSD), the symptoms of which have been hypothesized to be related to alterations in noradrenergic function. © 1996 Wiley‐Liss, Inc.

Betaxolol, a selective β1-adrenergic receptor antagonist, diminishes anxiety-like behavior during early withdrawal from chronic cocaine administration in rats

“…It is well established that the amygdala, a forebrain limbic region, is responsible for fear recognition (Davis, 2000;Charney, 2003) and mediating anxiety (Davis, 1992;Bremner et al, 1996;Tanaka et al, 2000;Charney, 2003) in humans and animals. Additionally, the amygdala is potently activated following administration and withdrawal from various drugs of abuse, including cocaine (Zhou et al, 2003;Pollandt et al, 2006), morphine (Maj et al, 2003;Watanabe et al, 2003b) and alcohol (Koob, 1999).…”

Monoamine Oxidase A Activity and Norepinephrine Level in Hippocampus Determine Hyperwheel Running in SPORTS Rats

“…Hippocampal neurotransmission controls memory, learning, stress responses, and behavior in humans and animals (Bremner et al, 1996;Cryan et al, 2004;Dietmar et al, 1998;Galeotti et al, 2004). The NE neurons derived from the locus ceruleus target hippocampus and release NE to modulate brain functions in response to changes in the environment (Bremner et al, 1996).…”

“…The NE neurons derived from the locus ceruleus target hippocampus and release NE to modulate brain functions in response to changes in the environment (Bremner et al, 1996). Exercise training is one of the environmental changes that enhance the metabolism and turnover of NE in the hippocampus (Dunn et al, 1996).…”

“…The hippocampus has a central role in regulating positive affect, learning, memory functions, and emotion (Cahill et al, 1994;LeDoux, 1994). The hippocampus is sensitive to stress and to physical exercise, both of which activate norepinephrine (NE) terminals deriving from the locus ceruleus (Bremner et al, 1996;Xu et al, 2000;Carter, 1997). Following exercise stimulation, a variety of changes in gene expression and NE metabolism occurred in the hippocampus (Bronikowski et al, 2004;Dunn et al, 1996;Rhodes et al, 2003).…”

Role of the cannabinoid system in the effects induced by nicotine on anxiety-like behaviour in mice

“…Nicotine anxiogenic-like responses could be mediated by the release of some neurotransmitters, such as glutamate and noradrenaline (Brazell et al 1991;Toth et al 1992;Sharp and Matta 1993;Fu et al 1998) which are known to facilitate stress/anxiety-related behaviour (Gray et al 1994;Guimaraes et al 1991;Jessa et al 1995;Onaka et al 1996). The stimulatory effects of nicotine on corticotrophin releasing factor and ACTH release (Okuda et al 1993;Bremner et al 1996;Herman and Cullinan 1997) Anxiety and emotional disorders seem to be an important factor for the establishment and maintenance of tobacco addiction (Pomerleau, 1986). Therefore, the anxiolytic effects induced by nicotine could be a key cause of failure in smoking cessation.…”