The effects of locally infused cholinergic agonists on extracellular levels of norepinephrine in the olfactory bulb of anesthetized rats were determined using in vivo microdialysis coupled with high-performance liquid chromatography and electrochemical detection. Using chronically implanted microdialysis probes, the basal norepinephrine level in the olfactory bulb was 0.55 pg/10 microl dialysate. Local infusion of K+ (30 mM) or the norepinephrine re-uptake inhibitor desipramine (1 microM) through the dialysis probe significantly increased basal norepinephrine levels. Focal activation of noradrenergic 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 the olfactory bulb increased basal norepinephrine levels by 134% of control, suggesting that endogenously released acetylcholine modulates norepinephrine 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) reduced norepinephrine levels (54% of control). These results demonstrate that basal norepinephrine release in the olfactory bulb is potently modulated by stimulation of local cholinergic receptors. Nicotinic receptors stimulate, and muscarinic receptors inhibit, norepinephrine release from locus coeruleus terminals.