Depression and anxiety: role of the locus coeruleus and corticotropin-releasing factor.

Based on studies of depression and anxiety using animal (rat) models, it is suggested that, contrary to a widely accepted theory, increased activity of locus coeruleus (LC) neurons does not appear to potentiate anxiety; instead, the influence of LC activity may be opposite to this. First, studies are described that indicate that behavioral changes resembling what is seen in human clinical depression occur in rats exposed to highly stressful conditions, and the research is then traced, which links this stress-induced depression to disturbance of normal noradrenergic regulation of LC activity. Second, the potential role of corticotrophin releasing factor (CRF) in stress-induced behavioral depression is explored. CRF infused into the LC did not produce behavioral depression in the swim test but did increase anxiety; by comparison, CRF infused into the parabrachial nucleus lateral to LC increased both depression and anxiety. Finally, to further explore the relationship between LC activity and anxiety, drugs were infused into LC region to attempt to specifically activate or depress firing of LC neurons. In contrast to expectations, infusion to decrease firing of LC cells increased anxious behavior, while infusion to increase firing decreased anxious behavior. Several other studies are discussed that point to a similar conclusion. It is suggested that, at least in rats, the capacity of stress-inducing or aversive stimuli to activate LC neurons does not potentiate anxiety under environmental conditions that elicit this response, but, rather, the increased activity of the LC/dorsal noradrenergic system under such conditions may exert a counterbalancing, antianxiety influence.