Peripheral induction of burst firing in locus coeruleus neurons by nicotine mediated via excitatory amino acids.
The effect of systemic nicotine administration (50 micrograms kg-1 i.v.) on the activity of brain noradrenaline neurons in the locus coeruleus (LC) of chloral hydrate-anesthetized rats was analyzed with single cell recording techniques and quantitative computer assessment of firing rate, degree of bursting, and regularity of firing. Nicotine caused an increased firing rate of the cells, with an average time of onset of 1.7 s. An increase in burst activity was observed, as well as deregularization of the firing pattern. Intraventricularly administered kynurenic acid (1 mumol), an antagonist of excitatory amino acids (EAA), did not change the firing rate of the LC cells, but did induce a marked regularization of their firing pattern into a pacemaker-like activity and completely abolish burst firing. The EAA antagonist also blocked all of the above effects of nicotine on the LC neurons as well as their typical burst-activation response to a peripheral, noxious stimulus such as paw-pinch. Since the circulation time in the rat is about 20 s, these results provide unequivocal evidence for a peripheral site of origin for the rapid LC activation induced by systemic nicotine administration. The data also allow the conclusion that the nicotine-induced LC activation is indirect and dependent on EAA in brain. Our results provide evidence for a tonically active EAA input to the LC, being of importance for induction of changes in the spontaneous, pacemaker activity of LC neurons into burst firing or more irregular firing patterns. It is suggested that the LC activation by nicotine may be significant in relation to tobacco dependence.
Tung
C S
CS
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Ugedo
L
L
Grenhoff
J
J
Engberg
G
G
Svensson
T H
TH
D000200:Action Potentials / Q000187:drug effects; D000596:Amino Acids / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D007275:Injections, Intravenous; D007736:Kynurenic Acid / Q000494:pharmacology; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D009538:Nicotine; D007736:Kynurenic Acid