Elsevier

Neuroscience

Volume 101, Issue 4, 30 November 2000, Pages 1071-1082
Neuroscience

Role of locus coeruleus in foot shock-evoked fos expression in rat brain

https://doi.org/10.1016/S0306-4522(00)00372-9Get rights and content

Abstract

The robust activation of locus coeruleus neurons in response to a variety of stressors, in conjunction with the widespread outputs of the locus coeruleus, suggest that the locus coeruleus may be important in mediating responses to stress. Previous studies in rats have demonstrated that exposure to foot shock elicits Fos expression, a marker of neuronal activation, in the locus coeruleus and other brain sites. In order to evaluate the involvement of the locus coeruleus in foot shock-induced activation of other brain sites, shock-induced Fos expression was examined in the locus coeruleus and other brain areas known to be activated by foot shock, following direct inhibition of the locus coeruleus by local infusion of muscimol, a GABA agonist, prior to foot shock. Control rats received infusions of artificial cerebrospinal fluid into the locus coeruleus or muscimol into areas outside of locus coeruleus. Rats infused with artificial cerebrospinal fluid and then exposed to foot shock had significant increases in Fos expression in several brain areas, including locus coeruleus, nucleus O, several subdivisions of the hypothalamus, subnuclei of amygdala, bed nucleus of the stria terminalis and cingulate cortex. Inhibition of the locus coeruleus prior to foot shock significantly inhibited Fos expression in the locus coeruleus, nucleus O, some subdivisions of the hypothalamus including the magnocellular and medial parvicellular paraventricular hypothalamic nucleus, subnuclei of amygdala, and cingulate cortex. In contrast, inhibition of the locus coeruleus did not affect shock-induced Fos expression in other areas, including certain subdivisions of the hypothalamus and bed nucleus of the stria terminalis.

We suggest that foot shock may activate multiple pathways, with activation of certain discrete nuclei requiring input from the locus coeruleus and activation of others occurring independently of locus coeruleus input.

Section snippets

Animals and surgical procedures

Adult, male Sprague–Dawley rats (281–430 g; Zivic Miller, Zelienople, PA, USA) were individually housed in stainless steel cages. Rats were maintained on a 12-h light/dark cycle with food and water available ad libitum. All procedures conformed to NIH guidelines and were approved by the Institutional Animal Care and Use Committee at The University of Pittsburgh. Two to five days after arrival, rats were anesthetized with halothane and stereotaxic procedures were used to implant bilateral guide

Injection sites

Histological examination of tissue was used to document cannula placement. A typical LC microinjection site in a non-shocked rat in which aCSF was infused directly into the LC is shown in Fig. 1. The high level of Fos expression in the area immediately surrounding the cannula tracts was noted in all rats that received microinjections of either aCSF or muscimol and occurred when microinjections were made into the LC or into areas adjacent to the LC. Therefore, Fos expression in the LC was

DISCUSSION

In an effort to elucidate the role of the LC in stress-evoked responses, the present study sought to determine the effect of acute inhibition of the LC on foot shock-induced Fos expression throughout the rat brain. The key finding of the present study is that injection of the GABA agonist, muscimol, into the LC prevented or attenuated shock-induced Fos expression in many brain sites that express Fos in response to foot shock. These findings suggest that the LC may be an important component of

Conclusion

The present study has demonstrated that functional blockade of the LC prevented or attenuated foot shock-evoked Fos expression in several discrete brain areas previously shown to be activated in response to stress. Importantly, direct inhibition of the LC did not alter the response of all brain sites to foot shock stress, thereby demonstrating that this response to LC inhibition was not global. Thus, it seems that stress-evoked activation of LC neurons is necessary for the full activation of

Acknowledgements

This work was supported by PHS grants MH43411 and MH29670, and NIH Postdoctoral Training Award MH18903.

References (41)

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