Sg. Matta et al., SELECTIVE ADMINISTRATION OF NICOTINE INTO CATECHOLAMINERGIC REGIONS OF RAT BRAIN-STEM STIMULATES ADRENOCORTICOTROPIN SECRETION, Endocrinology, 133(6), 1993, pp. 2935-2942
Nicotine (Nic) is a potent stimulus for ACTH secretion, and this respo
nse appears to be mediated by central catecholamine secretion. We have
previously shown that fourth ventricular administration of Nic rapidl
y elevated plasma ACTH levels, that a nicotinic cholinergic antagonist
, mecamylamine, instilled into the fourth ventricle inhibited the ACTH
response to iv Nic, and that Nic stimulated norepinephrine secretion
in the hypothalamic paraventricular nucleus. Thus, the present investi
gations sought to identify Nic-responsive regions in the brainstem tha
t give rise to ascending catecholaminergic afferents resulting in ACTH
secretion. Chronic brain and jugular cannulae were implanted, and Nic
(50 nl over 30 sec) was infused into the locus coeruleus (LC), nucleu
s of the solitary tract (NTS -C2 or -A2 regions), C1, or A1 cell regio
ns of freely moving, adult male rats. Injection of Nic (free base, 0.2
5-10 mug) into either the C2 or A2 region of NTS resulted in a dose-de
pendent increase in plasma ACTH. In contrast, C1 was unresponsive and
A1 only showed responses to the highest doses of Nic (5 or 10 mug). In
LC, Nic in doses of 2.5 mug or higher was required to elevate plasma
ACTH. This dose is approximately 10-fold greater than that required in
NTS-A2. Finally, mecamylamine (0.25 mg/kg body wt, iv), administered
2 min before Nic, abolished the ACTH responses in both C2 and A2 and s
ignificantly reduced the 7-min peak ACTH response in LC (P < 0.05). In
summary, microinjection of Nic selectively activated the brainstem re
gions under investigation, with a rank order of sensitivity to Nic tha
t was NTS-A2 > NTS-C2 > LC > A1 > C1 = cerebrospinal fluid. Therefore,
systemically administered Nic appears to activate multiple catecholam
inergic brainstem regions that are involved in mediating ACTH secretio
n.