Coordinate Regulation of the Cyclic AMP System with Firing Rate and Expression of Tyrosine Hydroxylase in the Rat Locus Coeruleus: Effects of Chronic Stress and Drug Treatments
Abstract
Recent studies have demonstrated that chronic stress increases the firing rate and expression of tyrosine hydroxylase (TH) in neurons of the locus coeruleus (LC), the major noradrenergic nucleus in brain. The present study was undertaken to examine the influence of chronic stress and other treatments known to influence the activity of LC neurons on the cyclic AMP (cAMP) second messenger system in these neurons. Chronic (5 days) cold exposure significantly increased levels of TH immunoreactivity in the LC, as previously reported, but not in substantia nigra (SN) or ventral tegmentum (VT), two dopaminergic nuclei studied for comparison. Chronic cold exposure increased levels of cAMP-dependent protein kinase activity in soluble, but not particulate, fractions of the LC, and increased basal and GTP- and forskolin-stimulated adenylate cyclase activity in this brain region. In contrast, levels of the protein kinase and adenylate cyclase in VT, SN, and frontal cortex were not significantly influenced by cold exposure. To study further the relationship between regulation of LC firing rate, TH expression, and the cAMP system in the LC, other treatments known to influence TH were examined. Reserpine treatment, shown previously to increase levels of TH, was found to increase both LC firing rate and levels of soluble cAMP-dependent protein kinase activity in the LC. 6-Hydroxydopamine, shown previously to increase levels of TH and firing rate of LC neurons, also increased soluble levels o…
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The actions of norepinephrine are exaggerated with chronic stress exposure: there is increased expression of the synthetic enzymes tyrosine hydroxylase and dopamine β-hydroxylase in noradrenergic neurons and axons in both rats and primates.
“The actions of norepinephrine are exaggerated with chronic stress exposure: there is increased expression of the synthetic enzymes tyrosine hydroxylase and dopamine β-hydroxylase in noradrenergic neurons and axons in both rats83–85 and primates86.”
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Self-citation
- Authors
- Melia, K. R., Rasmussen, K., Terwilliger, R. Z., Haycock, J. W., Nestler, E. J., & Duman, R. S.
- Affiliations
- Yale University (US)
- Eli Lilly (United States) (US)
- Louisiana State University (US)
- Corresponding author
- Duman, Ronald S.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1992-02
- Volume
- 58
- Issue
- 2
- Pages
- 494-502
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2027069212
- Cited by
- 133
- References
- 0
- Citations by year
- 2025: 2 · 2023: 1 · 2022: 2 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 5
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r29da005490-01a1)
- National Institute of Mental Health (2P01 MH25642, MH-45481, P01MH025642)
- National Institute on Drug Abuse (DA-05490)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- locus coeruleus, tyrosine hydroxylase, protein kinase A, adenylate cyclase, firing rate, chronic stress, cold exposure, reserpine, 6-hydroxydopamine, adrenalectomy, imipramine, noradrenergic neurons, substantia nigra, ventral tegmental area, dopaminergic neurons
- MeSH terms
- Cyclic AMP, Adrenalectomy, Animals, Antidepressive Agents, Chronic Disease, Electrophysiology, Locus Coeruleus, Male, Norepinephrine, Rats, Inbred Strains, Reserpine, Stress, Physiological, Tyrosine 3-Monooxygenase, Rats
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