Abstract
The locus coeruleus (LC) is the major noradrenergic nucleus in the brain and innervates
large segments of the neuraxis. LC neurons are thought to regulate states of attention
and vigilance as well as activity of the sympathetic nervous system. These neurons
also have been implicated in the actions of stress, antidepressants, and opiates on
the brain. Aided in part by the fact that the LC is relatively homogeneous, it has
been possible to understand some of the cellular and molecular mechanisms that control
their functional state. This review focuses on the role played by the cAMP pathway
in regulation of LC neurons, particularly after chronic perturbations. Thus, several
components of this intracellular signaling pathway are upregulated in the LC after
chronic stress or chronic opiate treatment, but downregulated after chronic antidepressant
treatment. LC neurons exhibit a pacemaker activity, which appears to be mediated,
at least in part, by a nonspecific cation current that is activated by protein kinase
A. As a result, stimuli that upregulate the cAMP pathway after chronic administration
(e.g., stress or opiates) increase the excitability of LC neurons, whereas stimuli
that downregulate the cAMP pathway (e.g., antidepressants) exert the opposite effect.
Such molecular adaptations could contribute to the behavioral plasticity that is associated
with these various conditions.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Single unit response of noradrenergic neurons in locus coeruleus of freely moving cats II. Adaptation to chronically presented stressful stimuli.J Neurosci. 1987; 7: 2844-2848
- Tolerance to locus coeruleus neurons to morphine and suppression of withdrawal response by clonidine.Nature. 1978; 267: 186-188
- Pertussis toxin blocks the outward currents evoked by opiate and α2-agonists in locus coeruleus neurons.Brain Res. 1986; 371: 390-394
- Pacemaker activity of locus coeruleus neurons.Brain Res. 1991; 556: 339-343
- Opiates suppress a resting sodium-dependent inward current and activate an outward potassium current in locus coeruleus neurons.J Neurosci. 1993; 13: 3525-3532
- QX-314 blocks the potassium but not the sodium-dependent component of the opiate response in locus coeruleus neurons.Brain Res. 1994; 639: 320-324
- Noradrenergic mechanisms in age-related cognitive decline.J Neural Transm. 1987; 24: 317-324
- Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle.J Neurosci. 1981; 1: 876-886
- Neuromodulation and cognitive performance.Adv Pharmacol. 1998; 42: 755-759
- Role of the locus coeruleus in emotional activation.Prog Brain Res. 1996; 107: 379-402
- Colocalization of mu opioid receptors with GIRK1 potassium channels in the rat brain.Receptors Channels. 1995; 3: 221-241
- Regulation of cAMP-dependent protein kinase subunit expression in CATH.a and SH-SY5Y cells.J Pharmacol Exp Ther. 1998; 286: 1058-1065
- Regulation of tyrosine hydroxylase promoter activity by chronic morphine in TH9.0-LacZ transgenic mice.J Neurosci. 1998; 18: 9989-9995
- Structure and function of voltage-gated ion channels.Ann Rev Biochem. 1995; 64: 493-531
- Afferent projections to the rat locus coeruleus as determined by a retrograde tracing technique.J Comp Neurol. 1978; 178: 1-16
- The Biochemical Basis of Neuropharmacology. 7th ed. Oxford, New York1996
- Cell-type specific regulation of CREB gene expression.J Neurochem. 1998; 71: 1865-1974
- Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons.Acta Physiol Scand. 1964; 62: 5-55
- RGS proteins and signaling by heterotrimeric G proteins.J Biol Chem. 1997; 27: 3871-3874
- Activation of locus coeruleus from nucleus paragigantocellularis.J Neurosci. 1988; 8: 3644-3657
- GABA-mediated inhibition of locus coeruleus from the dorsomedial rostral medulla.J Neurosci. 1989; 9: 2973-2981
- Impulse activity of locus coeruleus neurons in awake rats and monkeys is a function of sensory stimulation and arousal.Proc Natl Acad Sci U S A. 1980; 77: 3033-3037
- Nucleus locus coeruleus.Physiol Rev. 1983; 63: 844-914
- The alpha-2a noradrenergic agonist, guanfacine, improves delayed response performance in young adult rhesus monkeys.Psychopharmacology. 1998; 136: 8-14
- Localizations of alpha 1 and beta 1 subunits of soluble guanylate cyclase in the rat brain.Mol Brain Res. 1993; 20: 335-344
- Regulators of G protein signaling.J Neurosci. 1997; 17: 8024-8037
- Neuronal activity of the locus coeruleus in awake Macaca arctoides.Exp Neurol. 1984; 84: 701-708
- Identification of MARPP-58, a morphine- and cyclic AMP-regulated phosphoprotein of 58 kD, as tyrosine hydroxylase.J Neurosci. 1990; 10: 2635-2645
- The time course of noradrenergic pre- and postsynaptic activity during chronic desipramine treatment.Eur J Pharmacol. 1979; 68: 41-47
- Synchronous activity in locus coeruleus results from dendritic interactions in pericoerulear regions.J Neurosci. 1996; 16: 5196-5204
- Unique and cell-type-specific tyrosine hydroxylase gene expression.Adv Pharmacol. 1998; 42: 33-36
- Long-term glutamate desensitization in locus coeruleus neurons and its role in opiate withdrawal.Brain Res. 1995; 689: 111-121
- Elevated basal firing rates of locus coeruleus neurons in brain slices from opiate-dependent rats.Eur J Pharmacol. 1992; 211: 47-53
- Neural substrates of opiate withdrawal.Trends Neurosci. 1992; 15: 186-191
- CREB in the locus coeruleus.J Neurosci. 1997; 17: 7890-7901
- Afferent projections to the rat locus coeruleus demonstrated by retrograde and anterograde tracing with cholera-toxin B subunit and Phaseolus vulgaris leucoagglutinin.Neuroscience. 1995; 65: 119-160
- Localization of adenylyl and guanylyl cyclase in rat brain by in situ hybridization.J Neurosci. 1992; 12: 3350-3360
- Chronic morphine administration causes region-specific increase of brain type VIII adenylyl cyclase mRNA.Eur J Pharmacol. 1994; 268: 215-221
- Chronic imipramine treatment normalizes levels of tyrosine hydroxylase in the locus coeruleus of chronically stressed rats.Psychopharmacology. 1992; 108: 23-26
- Coordinate regulation of the cyclic AMP system with firing rate and expression of tyrosine hydroxylase in the rat locus coeruleus.J Neurochem. 1992; 58: 494-502
- The 5′-flanking region of the mouse adenylyl cyclase type VIII genes imparts brain-region specific expression in transgenic mice.J Neurosci. 1999; 19: 2051-2058
- Molecular mechanisms of drug addiction.J Neurosci. 1992; 12: 2439-2450
- Molecular and cellular basis of addiction.Science. 1997; 278: 58-63
- Region-specific regulation of RGS4 (regulator of G protein signaling protein type 4) in brain by stress and glucocorticoids.J Neurosci. 1999; 19: 3674-3680
- Mu and delta receptors belong to a family of receptors that are coupled to potassium channels.Proc Natl Acad Sci U S A. 1987; 84: 5487-5491
- Tricyclic antidepressants.Eur J Pharmacol. 1975; 32: 302-312
- Elevated tyrosine hydroxylase in the locus coeruleus of suicide victims.J Neurochem. 1994; 62: 680-685
- Nitric oxide and carbon monoxide activate locus coeruleus neurons through a cGMP-dependent protein kinase.J Neurosci. 1996; 16: 1389-1399
- Single unit activity of locus coeruleus neurons in the freely moving cat. I. During naturalistic behaviors and in response to simple and complex stimuli.Brain Res. 1986; 371: 324-334
- Modulation of tyrosine hydroxylase gene expression in rat brain and adrenals by exposure to cold.J Neurosci Res. 1988; 20: 32-37
- G protein interaction with K+ and Ca2+ channels.Trends Pharmacol Sci. 1997; 18: 8-11
- Opioid receptor-coupled G-proteins in rat locus coeruleus membranes.Brain Res. 1997; 746: 10-18
- Effects of chronic treatment with delta9-tetrahydrocannabinol on cannabinoid-stimulated [35S]GTPgammaS autoradiography in rat brain.J Neurosci. 1996; 16: 8057-8066
- Peripheral, autonomic regulation of locus coeruleus noradrenergic neurons in brain.Psychopharmacology. 1987; 92: 1-7
- The locus coeruleus.Brain Res. 1976; 110: 39-56
- Cloning and functional expression of a novel rat brain sodium channel with a divergent domain III-IV linker and an EEKE pore region.Soc Neurosci Abs. 1998; 24: 1323
- Chronic morphine administration increases β-adrenergic receptor kinase (βARK) levels in the rat locus coeruleus.J Neurochem. 1994; 63: 1983-1986
- Activation of the locus coeruleus brain noradrenergic system during stress.Adv Pharmacol. 1998; 42: 781-784
- Antidepressant actions on brain noradrenergic neurons.J Pharmacol Exp Ther. 1990; 253: 833-840
- Excitation of locus coeruleus neurons by vasoactive intestinal peptide.J Neurosci. 1990; 10: 3335-3343
- Increased tyrosine hydroxylase activity in the locus coeruleus of rat brain stem after reserpine treatment and cold stress.Brain Res. 1974; 70: 547-552
Article info
Publication history
Accepted:
June 10,
1999
Received in revised form:
April 22,
1999
Received:
March 2,
1999
Identification
Copyright
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
