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Cited by 12Smoking Behavior and CessationNeurotransmitter Receptor Influence on BehaviorNicotinic Acetylcholine Receptors Study

Age-dependent effects of initial exposure to nicotine on serotonin neurons

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Bang, S.J., Commons, K.G.·2011·Neuroscience
DOI 10.1016/j.neuroscience.2011.01.032PMC PMC3059362
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Abstract

Adolescence is a critical vulnerable period during which exposure to nicotine greatly enhances the possibility to develop drug addiction. Growing evidence suggests that serotonergic (5-HT) neurotransmission may contribute to the initiation and maintenance of addictive behavior. As the dorsal raphe (DR) and median raphe (MnR) nuclei are the primary 5-HT source to the forebrain, the current study tested the hypothesis that there are age-dependent effects of acute nicotine administration on activation of 5-HT neurons within these regions. Both adolescent (Postnatal day 30) and adult (Postnatal day 70) male Sprague-Dawley rats received subcutaneous injection of either saline or nicotine (0.2, 0.4, or 0.8 mg/kg). Subsequently, the number of 5-HT cells that were double-labeled for Fos and tryptophan hydroxylase was counted in seven subregions within the DR and the entire MnR. The results show that acute nicotine injection induces Fos expression in 5-HT neurons in a region-specific manner. In addition, adolescents show broader regional activations at either a lower (0.2 mg/kg) and a higher (0.8 mg/kg) dose of nicotine, displaying a unique U-shape response curve across doses. In contrast, 5-HT cells with activated Fos expression were restricted to fewer regions in adults, and the patterns of expression were more consistent across doses. The results reveal dose-dependent effects of nicotine during adolescence with apparent sensitization at different ends of the dosage spectrum examined compared to adults. These data indicate that initial exposure to nicotine may have unique effects in adolescence on the ascending 5-HT system, with the potential for consequences on the affective-motivational qualities of the drug and the subsequent propensity for repeated use.

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  • Serotonin systems are uniquely sensitive to nicotine during adolescence.

    “Serotonin systems are also uniquely sensitive to nicotine during adolescence (Slotkin & Seidler, 2009; Bang & Commons, 2011; Dao et al., 2011).”

    From Unique, long-term effects of nicotine on adolescent brain. (2020) · cites this paper as Bang & Commons, 2011

  • Animal studies point to the unique sensitivity of the adolescent serotonin system to regulation by nicotine.

    “Although dopamine is clearly involved, animal studies also point to the unique sensitivity of the adolescent serotonin system to regulation by nicotine (Shearman et al. 2008; Bang & Commons, 2011; Dao et al. 2011).”

    From <scp>N</scp> icotine and the adolescent brain (2015) · cites this paper as Bang & Commons, 2011

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  1. Abrams JK Johnson PL Hay-Schmidt A Mikkelsen JD Shekhar A Lowry CA 2005 Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs Neuroscience 133 4 983 997 15916857
  2. Adriani W Macrì S Pacifici R Laviola G 2002 Peculiar vulnerability to nicotine oral self-administration in mice during early adolescence Neuropsychopharmacology 27 2 212 224 12093595
  3. Adriani W Granstrem O Macri S Izykenova G Dambinova S Laviola G 2004 Behavioral and neurochemical vulnerability during adolescence in mice: studies with nicotine Neuropsychopharmacology 29 869 878 14666123
  4. Andén NE Dahlström A Fuxe K Larsson K 1965 Mapping out of catecholamine and 5-hydroxytryptamine neurons innervating the telencephalon and diencephalon Life Sci 4 13 1275 1279 5849269
  5. Awtry TL Werling LL 2003 Acute and chronic effects of nicotine on serotonin uptake in prefrontal cortex and hippocampus of rats Synapse 50 3 206 211 14515338
  6. Azmitia EC Segal M 1978 An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat J Comp Neurol 179 3 641 667 565370
  7. Bar-Peled O Gross-Isseroff R Ben-Hur H Hoskins I Groner Y Biegon A 1991 Fetal human brain exhibits a prenatal peak in the density of serotonin 5-HT1A receptors Neurosci Lett 127 2 173 176 1831889
  8. Barnes NM Sharp T 1999 A review of central 5-HT receptors and their function Neuropharmacology 38 8 1083 1152 10462127
  9. Breslau N Peterson EL 1996 Smoking cessation in young adults: age at initiation of cigarette smoking and other suspected influences Am J Public Health 86 2 214 220 8633738 PMC1380330
  10. Carboni E Acquas E Leone P Perezzani L Di Chiara G 1988 5-HT3 receptor antagonists block morphine- and nicotine-induced place-preference conditioning Eur J Pharmacol 151 1 159 160 3416924
  11. Chen J Millar WJ 1998 Age of smoking initiation: implications for quitting Health Rep 9 4 39-46 (Eng); 39-48 (Fre) 9836879
  12. Cheeta S Kenny PJ File SE 2000 The role of 5-HT1A receptors in mediating the anxiogenic effects of nicotine following lateral septal administration Eur J Neurosci 12 10 3797 3802 11029650
  13. Cheeta S Irvine EE Kenny PJ File SE 2001 The dorsal raphé nucleus is a crucial structure mediating nicotine’s anxiolytic effects and the development of tolerance and withdrawal responses Psychopharmacology (Berl) 155 1 78 85 11374339
  14. Cippitelli A Damadzic R Hansson AC Singley E Sommer WH Eskay R Thorsell A Heilig M 2010 Neuropeptide Y (NPY) suppresses yohimbine-induced reinstatement of alcohol seeking Psychopharmacology (Berl) 208 3 417 426 20012021
  15. Commons KG Connolley KR Valentino RJ 2003 A neurochemically distinct dorsal raphe-limbic circuit with a potential role in affective disorders Neuropsychopharmacology 28 2 206 215 12589373
  16. Curran T Morgan JI 1995 Fos: an immediate-early transcription factor in neurons J Neurobiol 26 3 403 412 7775973
  17. Dayas CV Liu X Simms JA Weiss F 2007 Distinct patterns of neural activation associated with ethanol seeking: effects of naltrexone Biol Psychiatry 61 8 979 989 17098214 PMC2831298
  18. Dillon KA Gross-Isseroff R Israeli M Biegon A 1991 Autoradiographic analysis of serotonin 5-HT1A receptor binding in the human brain postmortem: effects of age and alcohol Brain Res 554 1–2 56 64 1834306
  19. Dyck RH Cynader MS 1993 Autoradiographic localization of serotonin receptor subtypes in cat visual cortex: transient regional, laminar, and columnar distributions during postnatal development J Neurosci 13 10 4316 4338 8410190 PMC6576380
  20. Hollis JH Evans AK Bruce KP Lightman SL Lowry CA 2006 Lipopolysaccharide has indomethacin-sensitive actions on Fos expression in topographically organized subpopulations of serotonergic neurons Brain Behav Immun 20 6 569 577 16554144
  21. Imai H Steindler DA Kitai ST 1986 The organization of divergent axonal projections from the midbrain raphe nuclei in the rat J Comp Neurol 243 3 363 380 2419370
  22. Kenny PJ File SE Rattray M 2001 Nicotine regulates 5-HT(1A) receptor gene expression in the cerebral cortex and dorsal hippocampus Eur J Neurosci 13 6 1267 1271 11285026
  23. Koob GF Le Moal M 1997 Drug abuse: hedonic homeostatic dysregulation Science 278 5335 52 58 9311926
  24. Levin ED Lawrence S Petro A Horton K Seidler FJ Slotkin TA 2006 Increased nicotine self-administration following prenatal exposure in female rats Pharmacol Biochem Behav 85 3 669 674 17196243 PMC1797890
  25. Li X Rainnie DG McCarley RW Greene RW 1998 Presynaptic nicotinic receptors facilitate monoaminergic transmission J Neurosci 18 5 1904 1912 9465015 PMC6792622
  26. Michelsen KA Schmitz C Steinbusch HW 2007 The dorsal raphe nucleus—from silver stainings to a role in depression Brain Res Rev 55 2 329 342 17316819
  27. Mihailescu S Guzmán-Marín R Domínguez Mdel C Drucker-Colín R 2002 Mechanisms of nicotine actions on dorsal raphe serotoninergic neurons Eur J Pharmacol 452 1 77 82 12323387
  28. Paxinos G Watson C 2005 The rat brain in stereotaxic coordinates —the new coronal set 5 Academic Press Sydney
  29. Petrov T Krukoff TL Jhamandas JH 1992 The hypothalamic paraventricular and lateral parabrachial nuclei receive collaterals from raphe nucleus neurons: a combined double retrograde and immunocytochemical study J Comp Neurol 318 1 18 26 1583154
  30. Petrov T Krukoff TL Jhamandas JH 1994 Chemically defined collateral projections from the pons to the central nucleus of the amygdala and hypothalamic paraventricular nucleus in the rat Cell Tissue Res 277 2 289 295 7521791
  31. Plaza-Zabala A Martín-García E de Lecea L Maldonado R Berrendero F 2010 Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior J Neurosci 30 6 2300 2310 20147556 PMC2829191
  32. Ribeiro EB Bettiker RL Bogdanov M Wurtman RJ 1993 Effects of systemic nicotine on serotonin release in rat brain Brain Res 621 311 318 8242344
  33. Roche M Commons KG Peoples A Valentino RJ 2003 Circuitry underlying regulation of the serotonergic system by swim stress J Neurosci 23 3 970 977 12574426 PMC6741925
  34. Shearman E Fallon S Sershen H Lajtha A 2008 Nicotine-induced monoamine neurotransmitter changes in the brain of young rats Brain Res Bull 76 6 626 639 18598854
  35. Shram MJ Lê AD 2010 Adolescent male Wistar rats are more responsive than adult rats to the conditioned rewarding effects of intravenously administered nicotine in the place conditioning procedure Behav Brain Res 206 20 240 244 19765617
  36. Shram MJ Funk D Li Z Lê AD 2006 Periadolescent and adult rats respond differently in tests measuring the rewarding and aversive effects of nicotine Psychopharmacology (Berl) 186 2 201 208 16586088
  37. Slotkin TA Tate CA Cousins MM Seidler FJ 2006 Prenatal nicotine exposure alters the responses to subsequent nicotine administration and withdrawal in adolescence: Serotonin receptors and cell signaling Neuropsychopharmacology 31 11 2462 2475 16341021
  38. Summers KL Lippiello P Giacobini E 1996 A microdialysis study of the effects of the nicotinic agonist RJR-2403 on cortical release of acetylcholine and biogenic amines Neurochem Res 21 10 1181 1186 8923478
  39. Taioli E Wynder EL 1991 Effect of the age at which smoking begins on frequency of smoking in adulthood N Engl J Med 325 13 968 969 1881424
  40. Torres OV Tejeda HA Natividad LA O’Dell LE 2008 Enhanced vulnerability to the rewarding effects of nicotine during the adolescent period of development Pharmacol Biochem Behav 90 4 658 663 18571223 PMC2576495
  41. Toth E Sershen H Hashim A Vizi ES Lajtha A 1992 Effect of nicotine on extracellular levels of neurotransmitters assessed by microdialysis in various brain regions: role of glutamic acid Neurochem Res 17 265 271 1352387
  42. Turner DM 1975 Influence of route of administration on metabolism of [14C]nicotine in four species Xenobiotica 5 9 553 61 810976
  43. Van Bockstaele EJ Biswas A Pickel VM 1993 Topography of serotonin neurons in the dorsal raphe nucleus that send axon collaterals to the rat prefrontal cortex and nucleus accumbens Brain Res 624 1–2 188 198 8252391
  44. van der Kooy D Hattori T 1980 Dorsal raphe cells with collateral projections to the caudate-putamen and substantia nigra: a fluorescent retrograde double labeling study in the rat Brain Res 186 1 1 7 7357440
  45. Vertes RP Fortin WJ Crane AM 1999 Projections of the median raphe nucleus in the rat J Comp Neurol 407 4 555 582 10235645
  46. Wilmouth CE Spear LP 2004 Adolescent and adult rats’ aversion to flavors previously paired with nicotine Ann N Y Acad Sci 1021 462 464 15251930
  47. Xu Z Seidler FJ Ali SF Slikker W Jr Slotkin TA 2001 Fetal and adolescent nicotine administration: effects on CNS serotonergic systems Brain Res 914 1–2 166 178 11578609
  48. Xu Z Seidler FJ Cousins MM Slikker W Jr Slotkin TA 2002 Adolescent nicotine administration alters serotonin receptors and cell signaling mediated through adenylyl cyclase Brain Res 951 2 280 292 12270507

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Sorted by citations

Authors
Bang, S. J., & Commons, K. G.
Affiliations
Boston Children's Hospital (US)
ORCID
Commons, K.G.
Venue
Neuroscience
Publisher
Elsevier BV
Published
2011-04
Volume
179
Pages
1-8
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2011.01.032
PMC
PMC3059362
OpenAlex
W1983755815
Cited by
12
References
11
Citations by year
2024: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1
FWCI
0.65
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Drug Abuse (DA‐021801, R01DA021801)
Topics
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
nicotine, serotonergic neurons, dorsal raphe nucleus, median raphe nucleus, adolescence, age-dependent effects, Fos expression, tryptophan hydroxylase, acute nicotine administration, dose-response relationship, drug addiction, serotonergic system, sensitization
MeSH terms
Age Factors, Animals, Immunohistochemistry, Male, Neurons, Nicotine, Raphe Nuclei, Serotonin, Behavior, Addictive, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Nicotinic Agonists, Rats

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