Premium
Sensitization to the neuroendocrine, central monoamine and behavioural effects of murine tumor necrosis factor‐α: peripheral and central mechanisms
Author(s) -
Hayley S.,
Wall P.,
Anisman H.
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.01936.x
Subject(s) - endocrinology , medicine , locus coeruleus , corticosterone , sensitization , monoamine neurotransmitter , central nucleus of the amygdala , dopamine , amygdala , serotonin , hypothalamus , norepinephrine , chemistry , central nervous system , hormone , immunology , receptor
Systemic administration of murine tumour necrosis factor‐α (mTNF‐α; 0.1–2.0 µg, i.p.) dose‐dependently increased plasma corticosterone and augmented monoamine utilization within the paraventricular nucleus of the hypothalamus (PVN), locus coeruleus, medial prefrontal cortex (PFC), central and medial amygdala. A time‐dependent sensitization was induced in mice, wherein reexposure to mTNF‐α 28 days (but not 1 day) following the initial cytokine treatment provoked marked signs of illness (diminished activity, ptosis, piloerection) and increased plasma corticosterone levels. Serotonin (5‐HT) activity was augmented upon mTNF‐α reexposure at the 1‐ or 28‐day intervals in the PFC and medial amygdala, respectively. Intracerebroventricular (i.c.v.; 1–500 ng) mTNF‐α did not promote illness, but modestly increased plasma corticosterone levels. Neither the illness nor the corticosterone changes were subject to a sensitization upon i.c.v. cytokine reexposure. Acute i.c.v. mTNF‐α increased norepinephrine (NE), 5‐HT and dopamine (DA) activity within the PVN and median eminence/arcuate nucleus complex (ME/ARC), and NE utilization within the central amygdala. Subsequent i.c.v. mTNF‐α further enhanced the hypothalamic monoamine variations. Finally, systemic (i.p.) mTNF‐α pretreatment did not proactively influence sickness or corticosterone responses upon later i.c.v. cytokine challenge, but augmented locus coeruleus NE activity and 5‐HT and DA utilization within the ME/ARC. It is suggested that the sensitization with respect to sickness and corticosterone activity in response to mTNF‐α reflect the involvement of peripheral mechanisms. Moreover, it appears that mTNF‐α promotes central neurochemical plasticity through independent central and peripheral mechanisms.