Elsevier

Neuroscience

Volume 93, Issue 2, July 1999, Pages 611-617
Neuroscience

Evidence for cholinergic regulation of basal norepinephrine release in the rat olfactory bulb

https://doi.org/10.1016/S0306-4522(99)00169-4Get rights and content

Abstract

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 μl dialysate. Local infusion of K+ (30 mM) or the norepinephrine re-uptake inhibitor desipramine (1 μM) 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.

Section snippets

Materials

Soman (pinacolyl methylphosphonofluoridate) was supplied by the U.S. Army Institute for Chemical Defense (Aberdeen Proving Ground, Maryland). Acetylcholine (ACh) hydrochloride, pilocarpine hydrochloride, desipramine hydrochloride, (−)-nicotine, monochloroacetic acid, octyl sodium sulfate, NE bitartrate and ascorbate oxidase (EC 1.10.3.3) were obtained from Sigma Chemical Co. (St Louis, MO).

Microdialysis probe implantation

Experimental procedures were conducted so as to minimize animal suffering and the number of animals used.

Basal and locus coeruleus-evoked norepinephrine levels in the olfactory bulb

The basal level of NE in the olfactory bulb of anesthetized rats recovered by in vivo microdialysis was 0.55±0.11 pg/10 μl dialysate (n=21). In the first set of experiments, we determined if extracellular NE levels were modified by stimuli known to increase transmitter release. First, NE levels were measured before, during and after local depolarization by infusing a high K+ ACSF solution through the microdialysis probe. As shown in Fig. 1A, infusion of ACSF (pH 7.4) containing 30 mM K+ for 10 min

Discussion

The major finding of this study is that ACh regulates extracellular NE levels in the olfactory bulb via actions on nicotinic and muscarinic receptors. Nicotinic and muscarinic receptors in the olfactory bulb appear to exert opposing actions, as local perfusion of the nicotinic receptor agonist nicotine increased, and the muscarinic receptor agonist pilocarpine decreased, NE levels. Local infusion of ACh or the AChE inhibitor soman increased NE levels, suggesting that the action of increased ACh

Acknowledgements

We thank Mrs Mingxin Song for technical assistance. This work was supported by U.S. Army Contract DAMD-17-95-C-5031, and PHS grants DC02588 and NS24698.

References (49)

  • S.P Hunt et al.

    Some observations on the binding patterns of α-bungarotoxin in the central nervous system of the rat

    Brain Res.

    (1978)
  • P Kasa et al.

    Synaptic and non-synaptic cholinergic innervation of the various types of neurons in the main olfactory bulb of the adult rat: immunocytochemistry of choline acetyltransferase

    Neuroscience

    (1995)
  • R.M Kobayashi et al.

    Regional distribution of muscarinic cholinergic receptors in rat brain

    Brain Res.

    (1978)
  • W.A.A Kunze et al.

    Effect of stimulating the nucleus of the horizontal limb of the diagonal band on single unit activity in the olfactory bulb

    Neuroscience

    (1991)
  • W.A.A Kunze et al.

    Intracellular responses of olfactory bulb granule cells to stimulating the horizontal diagonal band nucleus

    Neuroscience

    (1992)
  • L McKay et al.

    Ascorbic acid oxidase speeds up analysis from catecholamines, indoleamines and their metabolites in brain tissue using high-performance liquid chromatography with electrochemical detection

    J. Chromat.

    (1984)
  • L Schwartz et al.

    Synergy between membrane depolarization and muscarinic receptor activation leads to potentiation of neurotransmitter release (II)

    Brain Res.

    (1989)
  • M.T Shipley et al.

    Surprisingly rich projection from locus coeruleus to the olfactory bulb in the rat

    Brain Res.

    (1985)
  • G.N Smagin et al.

    Corticotropin-releasing factor administered into locus coeruleus, but not the parabrachial nucleus, stimulates norepinephrine release in the prefrontal cortex

    Brain Res. Bull.

    (1995)
  • T.C Westfall

    Effect of muscarinic agonists on the release of 3H-norepinephrine and 3H-dopamine by potassium and electrical stimulation from rat brain slices

    Life Sci.

    (1974)
  • T.C Westfall

    Effect of nicotine and other drugs on the release of 3H-norepinphrine and 3H-dopamine from rat brain slices

    Neuropharmacology

    (1974)
  • Abercrombie E. D. and Finlay J. M. (1991) Monitoring extracellular norepinephrine in brain using in vivo microdialysis...
  • Aston-Jones G., Shipley M. T. and Grzanna R. (1995) The locus coeruleus. In The Rat Nervous System, 2nd edn (ed....
  • A.L Curtis et al.

    Activation of the locus coeruleus noradrenergic system by intracoerulear microinfusion of corticotropin-releasing-factor: effects on discharge rate, cortical norepinephrine levels and cortical electroencephalograhic activity

    J. Pharmac. exp. Ther.

    (1997)
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