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

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.