The involvement of norepinephrine and microglia in hypothalamic and splenic IL-1beta responses to stress.
The noradrenergic system plays an integral role in the stress response and modulates expression of proinflammatory cytokines. Recent work from our laboratory and others has shown that certain stressors increase the expression of the proinflammatory cytokine interleukin-1beta (IL-1beta) in the hypothalamus and spleen. One goal of the following studies was to assess the role of norepinephrine in stress-elicited increases in IL-1beta. To do this, adult male Sprague-Dawley rats were injected with propranolol (20 mg/kg i.p.) or desipramine (20 mg/kg s.c.) and exposed to 80 inescapable footshocks (2.0 mA, 90 s variable ITI, 5 s each). We found that propranolol blocked the IL-1beta response to footshock in both the hypothalamus and the spleen, while the noradrenergic reuptake inhibitor desipramine significantly augmented the footshock-induced IL-1beta response in both of these sites. Our second goal was to determine whether these effects would also be blocked by administration of a putative microglial inhibitor (minocycline). Minocycline (40 mg/kg i.p.) completely reversed the footshock-induced increase in hypothalamic IL-1beta but had no effect on the IL-1beta response in the spleen. Moreover, lack of an effect of minocycline on conditioned fear responding suggests that the effect of this drug cannot be explained by nonspecific sedative properties produced by the drug. Together, these data suggest that NE powerfully modulates the hypothalamic and splenic IL-1beta response to stress, and that microglia may be a primary cellular source of central IL-1beta in response to footshock.
Blandino
Peter
P
Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, Binghamton, NY 13902-6000, USA.
Barnum
Christopher J
CJ
Deak
Terrence
T
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D008911:Minocycline / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*; D013315:Stress, Psychological / Q000503:physiopathology*
D018759:Adrenergic Uptake Inhibitors; D014151:Anti-Anxiety Agents; D000900:Anti-Bacterial Agents; D007375:Interleukin-1; D011433:Propranolol; D008911:Minocycline; D003891:Desipramine; D009638:Norepinephrine