Locus coeruleus activity levels

Several findings support this model. For instance, an early report suggested that there is a positive correlation between the density of (postsynaptic) jS-adrenoceptors in rat cortex and behavioural resistance to a mild environmental stress (novelty and frustration) but a negative correlation between these parameters when the stress is intensified (Stanford and Salmon 1992). More recently, it has been proposed that the phasic response of neurons in the locus coeruleus (which governs attentiveness ) depends on their tonic activity (which determines arousal). Evidence suggests that the relationship between these two parameters is described by a bell-shaped curve and so an optimal phasic response is manifest only at intermediate levels of tonic activity (Rajkowski et al. 1998). 

Goddard AW, Mason GF, Almai A, Rothman DL, Behar KL, Petroff OA, Charney DS, Krystal JH (2001) Reductions in occipital cortex GABA levels in panic disorder detected with Ih-magnetic resonance spectroscopy. Arch Gen Psychiatry 58 556-561 Grant MM, Weiss JM (2001) Effects of chronic antidepressant drug administration electroconvulsive shock on locus coeruleus electrophysiologic activity. Biol Psychiatry 49 117-129... 

The basic components of the fight-or-flight mechanism are depicted schematically in figure 7-B. As stressful events are perceived at the level of the cortex, lower brain areas become activated. In a sense, the limbic system is put on alert. Should ongoing perception result in a conclusion that there is imminent danger, a burst of excitation emanates from a cluster of nerve cell bodies in the brain stem called the locus coeruleus (LC). The LC has sometimes been called the adrenal gland of the brain. The LC nerve cells, which project to the limbic system, are mediated by the neurotransmitter norepinephrine. 

Cyclobenzaprine is a central-acting muscle relaxant that is commonly used to treat pain from injury, muscle spasms, and other painful musculoskeletal conditions. It is structurally related to first-generation tricyclic antidepressants such as imipramine and amitriptyline and appears to inhibit the uptake of norepinephrine in the locus coeruleus. Tricyclic compounds with norepinephrine reuptake-inhibiting properties have been shown to exert analgesic effects in chronic nerve and muscle pain by acting primarily within the central nervous system at brainstem as opposed to spinal cord levels, although their action on the latter may contribute to their overall skeletal muscle relaxant activity. The exact mechanism of action of cyclobenzaprine is unknown. 

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