Variations of nucleus accumbens dopamine and serotonin following systemic interleukin-1, interleukin-2 or interleukin-6 treatment.
The effects of systemically administered interleukin-1beta (1.0 microg), interleukin-6 (1.0 microg) and interleukin-2 (1.0 microg) on in vivo variations of monoamines were assessed in the nucleus accumbens. Administration of interleukin-1beta did not affect extracellular accumbal dopamine, provoked a modest rise of homovanillic acid, and prevented the decline of dihydroxyphenylacetic acid ordinarily seen in saline treated rats. Also, interleukin-1 provoked a modest increase of extracellular 5-hydroxyindoleacetic acid from the nucleus accumbens. Following exposure to the stress of a series of air-puffs, a still greater increase of accumbal 5-hydroxyindoleacetic acid was evident. In contrast to interleukin-1, systemic administration of interleukin-6 and interleukin-2 both induced marked reductions of interstitial dopamine levels. The air-puff exposure further enhanced these effects in rats that had received the cytokine treatment. As well, interleukin-6 and interleukin-2 were both found to reduce the homovanillic acid response associated with the stress, and interleukin-2 promoted a decline of homovanillic acid levels. Treatment with interleukin-6, like that of interleukin-1, prevented the decline of dihydroxyphenylacetic acid ordinarily observed over time, while interleukin-2 was without effect in this respect. Finally, interleukin-6 provoked a modest rise of 5-hydroxyindoleacetic acid, which was most apparent following air-puff exposure, while administration of interleukin-2 did not affect accumbal 5-hydroxyindoleacetic acid. It is suggested that the cytokines may influence the release of biogenic amines in the nucleus accumbens, but the profile of changes were cytokine-specific. As well, it appeared that the cytokines, particularly interleukin-1 and interleukin-6, may act synergistically with the stressor in promoting the amine variations. Systemic administration of cytokines clearly influenced monoamine activity at the nucleus accumbens, a region associated with both rewarding and aversive events. Thus, it may be expected that cytokine treatments may affect behavior. Moreover, it seems that the effects of interleukin-1 and interleukin-6 may be influenced by the presence of stressful stimuli. It ought to be underscored that although cytokines share features with the effects of stressors, most notably the variations of hypothalamic-pituitary-adrenal hormones, the pattern of central neurochemical changes elicited by the cytokines could be distinguished from the amine variations ordinarily associated with stressors.
Song
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C
Institute of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
Merali
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Z
Anisman
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H
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*
D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid