Role of central catecholamines in the modulation of corticotrophin-releasing factor mRNA during adjuvant-induced arthritis in the rat.
The development of adjuvant-induced arthritis in the rat is associated with an activation of the hypothalamo-pituitary-adrenal axis. In the Piebald-Viral-Glaxo strain of rat there is however a paradoxical decrease in corticotrophin-releasing factor (CRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and a decrease in CRF-41 peptide release into the hypophysial portal blood with increasing severity of disease. In the present study we have investigated the role of endogenous catecholamines within the PVN as possible inhibitory factors acting on CRF neurons during adjuvant-induced arthritis. Noradrenaline (NA) concentrations were approximately doubled in the PVN of arthritic animals. Depletion of endogenous catecholamines following direct 6-OHDA lesions of the PVN resulted in a significant depletion in PVN NA. The increase in NA observed in arthritic animals appears to have a protective role since depletion of NA increased the severity of the disease. Neither the increase in circulating levels of corticosterone nor the decrease in CRF mRNA in the PVN were prevented following NA depletion. Our results suggest that modification of central neurotransmitter systems are able to influence the severity of adjuvant-induced arthritis.
Harbuz
M S
MS
University Department of Medicine, Bristol Royal Infirmary.
Chover-Gonzalez
A J
AJ
Biswas
S
S
Lightman
S L
SL
Chowdrey
H S
HS
D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012720:Severity of Illness Index
D012333:RNA, Messenger; D016627:Oxidopamine; D003346:Corticotropin-Releasing Hormone; D009638:Norepinephrine