L. Givalois et al., INVOLVEMENT OF CENTRAL HISTAMINE IN THE EARLY PHASE OF ACTH AND CORTICOSTERONE RESPONSES TO ENDOTOXIN IN RATS, Neuroendocrinology, 63(3), 1996, pp. 219-226
The involvement of histaminergic transmission in the rapid and sustain
ed plasma ACTH and corticosterone (CORT) responses induced in consciou
s rats by intra-arterial infusions of 25 mu g . kg(-1) Escherichia col
i lipopolysaccharide (LPS) was investigated. LPS challenge produced a
rapid and transient increase (+ 62%) in the amount of histamine (HA) i
n the median eminence 15 min after LPS administration, which contraste
d with constant concentrations of plasma HA throughout the entire stud
y (up to 480 min). Blockade of histaminergic receptors by intra-arteri
al pretreatment with H-1 or H-2 antagonists (mepyramine, 1 mg/rat, and
cimetidine, 2 mg/rat), administered separately, did not affect either
ACTH or CORT responses to LPS. Pretreatment with the same doses of th
e two antagonists in combination very significantly but transiently im
paired the earliest phase (30 min) of the ACTH and CORT responses, wit
hout any apparent effect on the late phase of these responses. Pretrea
tment of the animals with an H-3-receptor agonist (R alpha-methylhista
mine dihydrochloride, 1 mg/rat) similarly blunted the early corticotro
pic responses to LPS, and also slightly depressed the long-lasting COR
T response. These findings support the view that activated central HA
transmission may be a key intermediate mechanism triggering the CRH41-
ACTH-CORT responses to LPS, in addition to the previously demonstrated
activating role of catecholaminergic afferences to the CRH41 neurons
during this early complex phase of corticotropic response to LPS.