Norepinephrine Secretion in the Hypothalamic Paraventricular Nucleus of Rats during Unlimited Access to Self-Administered Nicotine: An In Vivo Microdialysis Study
Open accessAbstract
Norepinephrine (NE) secretion within the hypothalamic paraventricular nucleus (PVN) is pivotal to endocrine and behavioral responses. Activation of NE afferents to PVN also is necessary for the hypothalamo-pituitary-adrenal axis response to passively administered nicotine. The mode of drug delivery is a critical determinant of the dynamics of neurotransmitter secretion, yet the PVN NE response to nicotine self-administration (SA) is unknown. Herein, rats housed in operant chambers had unlimited 23 hr access to self-administered nicotine. In vivo microdialysis of PVN NE was performed, collecting consecutive 7 min samples over 9 hr sessions during three phases of nicotine SA: acquisition (day 1); early maintenance, once stable rates of SA were achieved (day 9.2 +/- 0.6); later maintenance (day 18.6 +/- 0.8). On d1, nicotine animals had an increased percentage of SA episodes (SAEs) in which NE levels were elevated (80 vs 30% with saline; p < 0.01). By early maintenance, a fourfold increase in such episodes was observed in nicotine animals (p < 0.01), and the overall NE level was greater (1.30 +/- 0.24 vs 0.63 +/- 0.07 pg/10 microl in saline; p < 0.05); NE increased during the first, but not the last, SAE. The pattern was similar during later maintenance, although NE responsiveness declined (overall NE level, 0.96 +/- 0.19 in nicotine vs 0.52 +/- 0.08 pg/10 microl in saline; p < 0.05). Therefore, nicotine SAEs were associated with sustained increases in NE secretion during all three phases of SA. However, the reduced NE responsiveness observed both within the dialysis session in each phase and by later versus early maintenance is consistent with progression of partial daily desensitization of PVN NE secretion to nicotine SA. Therefore, in rats chronically self-administering nicotine, the drug stimulates sustained PVN NE secretion that may alter neuroendocrine and behavioral responses mediated by the PVN. Compared with studies of chronic human smokers, our nicotine SA model may reflect the CNS noradrenergic responses that occur during human cigarette smoking.
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Nicotine administration increases extracellular noradrenaline in various parts of the brain.
“Nicotine administration also increases the extracellular noradrenaline in various parts of the brain (32–35);”
From Tobacco addiction (2008) · cites this paper as [32]
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- Authors
- Fu, Y., Matta, S. G., Brower, V. G., & Sharp, B. M.
- Affiliations
- University of Tennessee Health Science Center (US)
- ORCID
- Sharp, Burt M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-11-15
- Volume
- 21
- Issue
- 22
- Pages
- 8979-8989
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762283
- OpenAlex
- W1863898741
- Cited by
- 66
- References
- 28
- Citations by year
- 2026: 1 · 2023: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 3
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Institute on Drug Abuse (R01DA003977, DA03977)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- norepinephrine, hypothalamic paraventricular nucleus, nicotine self-administration, noradrenergic neurotransmission, nicotine dependence, hypothalamic-pituitary-adrenal axis, nicotine withdrawal, cigarette smoking
- MeSH terms
- Animals, Behavior, Animal, Chromatography, High Pressure Liquid, Disease Models, Animal, Injections, Intravenous, Male, Nicotine, Norepinephrine, Paraventricular Hypothalamic Nucleus, Rats, Inbred Lew, Self Administration, Substance Abuse, Intravenous, Microdialysis, Rats
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