Evidence for cholinergic regulation of basal norepinephrine release in therat olfactory bulb

The effects of locally infused cholinergic agonists on extracellular levels of norepinephrine in the olfactory bulb of anesthetized rats were determin ed using in vivo microdialysis coupled with high-performance liquid chromat ography and electrochemical detection. Using chronically implanted microdia lysis probes, the basal norepinephrine level in the olfactory bulb was 0.55 pg/10 mu l dialysate. Local infusion of K+ (30 mM) or the norepinephrine r e-uptake inhibitor desipramine (1 mu M) through the dialysis probe signific antly increased basal norepinephrine levels. Focal activation of noradrener gic locus coeruleus neurons, the sole source of norepinephrine innervation of the olfactory bulb, increased norepinephrine levels by 247% of control. Local infusion of the acetylcholinesterase inhibitor soman (0.4 mM) into th e olfactory bulb increased basal norepinephrine levels by 134% of control, suggesting that endogenously released acetylcholine modulates norepinephrin e release. Intrabulbar infusion of acetylcholine (40 mM) or nicotine (40 mM ) increased norepinephrine levels (317% and 178% of control, respectively), while infusion of the muscarinic receptor agonist pilocarpine (40 mM) redu ced norepinephrine levels (54% of control). These results demonstrate that basal norepinephrine release in the olfactor y bulb is potently modulated by stimulation of local cholinergic receptors. Nicotinic receptors stimulate, and muscarinic receptors inhibit, norepinep hrine release from locus coeruleus terminals. (C) 1999 IBRO. Published by E lsevier Science Ltd.