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Cited by 15Smoking Behavior and CessationNicotinic Acetylcholine Receptors StudyMemory and Neural Mechanisms

Chronic fluoxetine ameliorates adolescent chronic nicotine exposure-induced long-term adult deficits in trace conditioning

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Connor, David A., Gould, Thomas J.·2017·Neuropharmacology
DOI 10.1016/j.neuropharm.2017.07.033PMC PMC5757519
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Abstract

Development of the brain, including the prefrontal cortex and hippocampus, continues through adolescence. Chronic nicotine exposure during adolescence may contribute to long-term deficits in forebrain-dependent learning. It is unclear if these deficits emerge immediately after exposure and if they can be ameliorated. In this study, C57BL/6J mice were treated with chronic nicotine (6.3 or 12.6 mg/kg/day) over 12 days beginning at adolescence, postnatal day (PND) 38, or adulthood, PND 56-63 ± 3. We investigated the effects of short-term (24 h) abstinence on trace fear conditioning and found that adult treatment resulted in deficits (6.3 and 12.6 mg/kg/day), but adolescent chronic nicotine treatment had no effect. In contrast, adolescent treatment with chronic nicotine (12.6 mg/kg/day) elicited a long-term (30 days) learning deficit, but adult chronic nicotine treatment did not. Using the elevated plus maze (EPM) we found no long-term changes in anxiety-related behavior after chronic nicotine exposure at either time-point. We investigated if chronic fluoxetine (FLX) could ameliorate adolescent chronic nicotine-associated long-term deficits in trace conditioning. We found that chronic FLX (160 mg/L) in drinking water ameliorated the long-term deficit in trace fear conditioning associated with nicotine exposure during adolescence. Additionally, in the same animals, we examined changes in total BDNF protein in the dorsal hippocampus (DH), ventral hippocampus (VH), and prefrontal cortex (PFC). Chronic FLX increased DH BDNF. Our data indicate nicotine administration during adolescence leads to late onset, long-lasting deficits in hippocampus-dependent learning that chronic FLX treatment ameliorate.

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  • Other research points to a role for hippocampus in ANE-induced cognitive deficits.

    “Other research points to a role for the hippocampus in ANE-induced cognitive deficits [196, 207, 208].”

    From Consequences of adolescent drug use (2023) · cites this paper as [207]

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References 98 · Cited by 15

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  1. Abreu-Villaça Y Nunes F Queiroz-Gomes F do E Manhães AC Filgueiras CC 2007 Combined exposure to nicotine and ethanol in adolescent mice differentially affects anxiety levels during exposure, short-Term, and long-term withdrawal Neuropsychopharmacology 33 599 610 10.1038/sj.npp.1301429 17460612 · DOI
  2. Abrous DN Adriani W Montaron M-F Aurousseau C Rougon G Moal ML Piazza PV 2002 Nicotine Self-Administration Impairs Hippocampal Plasticity J. Neurosci 22 3656 3662 11978841 PMC6758344
  3. Alme MN Wibrand K Dagestad G Bramham CR 2007 Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation Neural Plast 2007 e26496 10.1155/2007/26496 PMC2248427 18301726 · DOI · Paper page
  4. Altar CA Whitehead RE Chen R Wörtwein G Madsen TM 2003 Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain Biol Psychiatry 54 703 709 10.1016/S0006-3223(03)00073-8 14512210 · DOI · Paper page
  5. An JJ Gharami K Liao G-Y Woo NH Lau AG Vanevski F Torre ER Jones KR Feng Y Lu B Xu B 2008 Distinct role of long 3’ UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons Cell 134 175 187 10.1016/j.cell.2008.05.045 18614020 PMC2527207 · DOI
  6. Bailey SR Harrison CT Jeffery CJ Ammerman S Bryson SW Killen DT Robinson TN Schatzberg AF Killen JD 2009 Withdrawal symptoms over time among adolescents in a smoking cessation intervention: Do symptoms vary by level of nicotine dependence? Addict Behav 34 1017 1022 10.1016/j.addbeh.2009.06.014 19647373 PMC2739258 · DOI
  7. Balu DT Hoshaw BA Malberg JE Rosenzweig-Lipson S Schechter LE Lucki I 2008 Differential regulation of central BDNF protein levels by antidepressant and non-antidepressant drug treatments Brain Res 1211 37 43 10.1016/j.brainres.2008.03.023 18433734 PMC2394727 · DOI · Paper page
  8. Bath KG Jing DQ Dincheva I Neeb CC Pattwell SS Chao MV Lee FS Ninan I 2012 BDNF Val66Met Impairs Fluoxetine-Induced Enhancement of Adult Hippocampus Plasticity Neuropsychopharmacology 37 1297 1304 10.1038/npp.2011.318 22218094 PMC3306891 · DOI · Paper page
  9. Bramham CR Messaoudi E 2005 BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis Prog Neurobiol 76 99 125 10.1016/j.pneurobio.2005.06.003 16099088 · DOI · Paper page
  10. Chassin L Presson CC Sherman SJ Edwards DA 1990 The natural history of cigarette smoking: predicting young-adult smoking outcomes from adolescent smoking patterns Health Psychol. Off. J. Div. Health Psychol. Am. Psychol. Assoc 9 701 716 2286181
  11. Chen J Millar WJ 1998 Age of smoking initiation: implications for quitting Health Rep 9 39 46 (Eng); 39–48(Fre) 9836879
  12. Choi DC Gourley SL Ressler KJ 2012 Prelimbic BDNF and TrkB signaling regulates consolidation of both appetitive and aversive emotional learning Transl Psychiatry 2 e205 10.1038/tp.2012.128 23250006 PMC3565191 · DOI
  13. Cole RD Poole RL Guzman DM Gould TJ Parikh V 2014 Contributions of β2 subunit-containing nAChRs to chronic nicotine-induced alterations in cognitive flexibility in mice Psychopharmacology (Berl.) 232 1207 1217 10.1007/s00213-014-3754-4 25281224 PMC4361240 · DOI
  14. Connor DA Gould TJ 2016 The role of working memory and declarative memory in trace conditioning Neurobiol. Learn Mem 134 Part B 193 209 10.1016/j.nlm.2016.07.009 27422017 PMC5755400 · DOI
  15. Cunha C Brambilla R Thomas KL 2010 A simple role for BDNF in learning and memory? Front. Mol. Neurosci 3 10.3389/neuro.02.001.2010 PMC2821174 20162032 · DOI
  16. Davis JA Gould TJ 2007b Atomoxetine reverses nicotine withdrawal-associated deficits in contextual fear conditioning Neuropsychopharmacol 32 2011 9 10.1038/sj.npp.1301315 PMC2704605 17228337 · DOI
  17. Diniz CRaF Antero LS Resstel LBM Joca SRL 2014 P.4.C.009 Fluoxetine modulating dorsal and ventral hippocampal BDNF as responsible for facilitating extinction memory retention Eur. Neuropsychopharmacol 24 S610 S611 10.1016/S0924-977X(14)70979-4 · DOI
  18. Dulawa SC Holick KA Gundersen B Hen R 2004 Effects of chronic fluoxetine in animal models of anxiety and depression Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol 29 1321 1330 10.1038/sj.npp.l300433 15085085 · DOI
  19. Eiland L Romeo RD 2013 Stress and the developing adolescent brain Neuroscience, Stress and the Adolescent Brain 249 162 171 10.1016/j.neuroscience.2012.10.048 PMC3601560 23123920 · DOI
  20. ELBeltagy M Mustafa S Umka J Lyons L Salman A Gloria Tu C-Y Bhalla N Bennett G Wigmore PM 2010 Fluoxetine improves the memory deficits caused by the chemotherapy agent 5-fluorouracil Behav. Brain Res 208 112 117 10.1016/j.bbr.2009.11.017 19914299 · DOI
  21. Faraday MM Elliott BM Grunberg NE 2001 Adult vs. adolescent rats differ in biobehavioral responses to chronic nicotine administration Pharmacol. Biochem Behav., The Psychopharmacology of Nicotine 70 475 489 10.1016/S0091-3057(01)00642-6 11796147 · DOI
  22. Gould E Woolf NJ Butcher LL 1991 Postnatal development of cholinergic neurons in the rat: I Forebrain. Brain Res Bull 27 767 789 10.1016/0361-9230(91)90209-3 1664779 · DOI · Paper page
  23. Gould TJ Wehner JM 1999 Nicotine enhancement of contextual fear conditioning Behav. Brain Res 102 31 39 10.1016/S0166-4328(98)00157-0 10403013 · DOI
  24. Hajszan T MacLusky NJ Leranth C 2005 Short-term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus Eur. J. Neurosci 21 1299 1303 10.1111/j.1460-9568.2005.03968.x 15813939 · DOI
  25. Heldt SA Stanek L Chhatwal JP Ressler KJ 2007 Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories Mol Psychiatry 12 656 670 10.1038/sj.mp.4001957 17264839 PMC2442923 · DOI · Paper page
  26. Holliday ED Gould TJ 2017 Chronic nicotine treatment during adolescence attenuates the effects of acute nicotine in adult contextual fear learning Nicotine Tob Res 19 87 93 10.1093/ntr/ntw176 27613891 PMC6415932 · DOI
  27. Hoover WB Vertes RP 2007 Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat Brain Struct Funct 212 149 179 10.1007/s00429-007-0150-4 17717690 · DOI · Paper page
  28. Jin L Gao L-F Sun D-S Wu H Wang Q Ke D Lei H Wang J-Z Liu G-R 2016 Long-term ameliorative effects of the antidepressant fluoxetine exposure on cognitive deficits in 3 × TgAD mice Mol. Neurobiol 1 12 10.1007/s12035-016-9952-9 27324897 · DOI
  29. Kenney JW Raybuck JD Gould TJ 2012 Nicotinic receptors in the dorsal and ventral hippocampus differentially modulate contextual fear conditioning Hippocampus 22 1681 1690 10.1002/hipo.22003 22271264 PMC3343189 · DOI
  30. Kenny PJ File SE Rattray M 2000 Acute nicotine decreases, and chronic nicotine increases the expression of brain-derived neurotrophic factor mRNA in rat hippocampus Mol Brain Res 85 234 238 10.1016/S0169-328X(00)00246-1 11146126 · DOI
  31. Kim JJ Jung MW 2006 Neural circuits and mechanisms involved in Pavlovian fear conditioning: A critical review Neurosci. Biobehav. Rev., The Limbic Brain: Structure and Function 30 188 202 10.1016/j.neubiorev.2005.06.005 PMC4342048 16120461 · DOI · Paper page
  32. Korte M Kang H Bonhoeffer T Schuman E 1998 A role for BDNF in the late-phase of hippocampal long-term potentiation Neuropharmacology 37 553 559 9704996
  33. Laroche J Gasbarro L Herman JP Blaustein JD 2009 Reduced behavioral response to gonadal hormones in mice shipped during the peripubertal/adolescent period Endocrinology 150 2351 2358 10.1210/en.2008-1595 19131570 PMC2671909 · DOI
  34. Leão RM Cruz FC Marin MT Planeta C da S 2012 Stress induces behavioral sensitization, increases nicotine-seeking behavior and leads to a decrease of CREB in the nucleus accumbens Pharmacol. Biochem. Behav 101 434 442 10.1016/j.pbb.2012.01.025 22330674 · DOI
  35. Li W-L Cai H-H Wang B Chen L Zhou Q-G Luo C-X Liu N Ding X-S Zhu DY 2009 Chronic fluoxetine treatment improves ischemia-induced spatial cognitive deficits through increasing hippocampal neurogenesis after stroke J. Neurosci Res 87 112 122 10.1002/jnr.21829 18711744 · DOI
  36. Lyons L ElBeltagy M Umka J Markwick R Startin C Bennett G Wigmore P 2011 Fluoxetine reverses the memory impairment and reduction in proliferation and survival of hippocampal cells caused by methotrexate chemotherapy Psychopharmacology (Berl.) 215 105 115 10.1007/s00213-010-2122-2 21181126 PMC3072503 · DOI
  37. Malberg JE Eisch AJ Nestler EJ Duman RS 2000 Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus J. Neurosci 20 9104 9110 11124987 PMC6773038
  38. Mizuno K Dempster E Mill J Giese KP 2012 Long-lasting regulation of hippocampal BDNF gene transcription after contextual fear conditioning Genes Brain Behav 11 651 659 10.1111/j.1601-183X.2012.00805.x 22574690 PMC3982390 · DOI
  39. Molteni R Calabrese F Bedogni F Tongiorgi E Fumagalli F Racagni G Riva MA 2006 Chronic treatment with fluoxetine up-regulates cellular BDNF mRNA expression in rat dopaminergic regions Int. J. Neuropsychopharmacol 9 307 317 10.1017/S1461145705005766 16035958 · DOI · Paper page
  40. Mowla A Mosavinasab M Pani A 2007 Does fluoxetine have any effect on the cognition of patients with mild cognitive impairment?: A double-blind, placebo-controlled, clinical trial J. Clin Psychopharmacol 27 67 70 10.1097/JCP.0b013e31802e0002 17224716 · DOI
  41. O’Dell LE Bruijnzeel AW Ghozland S Markou A Koob GF 2004 Nicotine withdrawal in adolescent and adult rats Ann. N. Y. Acad Sci 1021 167 174 10.1196/annals.1308.022 15251887 · DOI
  42. O’Dell LE Torres OV Natividad LA Tejeda HA 2007 Adolescent nicotine exposure produces less affective measures of withdrawal relative to adult nicotine exposure in male rats Neurotoxicol Teratol., Exposures during adolescent development: are neurotoxic risks increased? 29 17 22 10.1016/j.ntt.2006.11.003 PMC3437755 17184972 · DOI
  43. Ortega LA Tracy BA Gould TJ Parikh V 2013 Effects of chronic low- and high-dose nicotine on cognitive flexibility in C57BL/6J mice Behav. Brain Res 238 134 145 10.1016/j.bbr.2012.10.032 23103711 PMC3513643 · DOI
  44. Patterson F Jepson C Loughead J Perkins K Strasser AA Siegel S Frey J Gur R Lerman C 2010 Working memory deficits predict short-term smoking resumption following brief abstinence Drug Alcohol Depend 106 61 10.1016/j.drugalcdep.2009.07.020 19733449 PMC2815089 · DOI
  45. Peters J Dieppa-Perea LM Melendez LM Quirk GJ 2010 Induction of fear extinction with hippocampal-infralimbic BDNF Science 328 1288 1290 10.1126/science.1186909 20522777 PMC3570764 · DOI · Paper page
  46. Phillips RG LeDoux JE 1992 Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning Behav. Neurosci 106 274 285 1590953
  47. Poole RL Connor DA Gould TJ 2014 Donepezil reverses nicotine withdrawal-induced deficits in contextual fear conditioning in C57BL/6J mice Behav. Neurosci 10.1037/bne0000003 PMC4172524 24911319 · DOI
  48. Portugal GS Gould TJ 2007 Bupropion dose-dependently reverses nicotine withdrawal deficits in contextual fear conditioning Pharmacol. Biochem Behav 88 179 187 10.1016/j.pbb.2007.08.004 17868796 PMC2049067 · DOI
  49. Raybuck JD Gould TJ 2010 The role of nicotinic acetylcholine receptors in the medial prefrontal cortex and hippocampus in trace fear conditioning Neurobiol. Learn. Mem 94 353 363 10.1016/j.nlm.2010.08.001 20727979 PMC2949463 · DOI
  50. Raybuck JD Gould TJ 2009 Nicotine withdrawal-induced deficits in trace fear conditioning in C57BL/6 mice - a role for high-affinity β2 subunit-containing nicotinic acetylcholine receptors Eur. J Neurosci 29 377 387 10.1111/j.l460-9568.2008.06580.x 19200240 PMC2746945 · DOI
  51. Reynolds LM Makowski CS Yogendran SV Kiessling S Cermakian N Flores C 2015 Amphetamine in adolescence disrupts the development of medial prefrontal cortex dopamine connectivity in a dcc-dependent manner Neuropsychopharmacology 40 1101 1112 10.1038/npp.2014.287 25336209 PMC4367452 · DOI
  52. Romeo RD McEwen BS 2006 Stress and the adolescent brain Ann. N. Y. Acad Sci 1094 202 214 10.1196/annals.1376.022 17347352 · DOI · Paper page
  53. Rubio FJ Ampuero E Sandoval R Toledo J Pancetti F Wyneken U 2013 Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield Front. Cell. Neurosci 7 10.3389/fncel.2013.00066 PMC3648695 23675317 · DOI · Paper page
  54. Saules KK Schuh LM Arfken CL Reed K Kilbey MM Schuster CR 2004 Double-blind placebo-controlled trial of fluoxetine in smoking cessation treatment including nicotine patch and cognitive-behavioral group therapy Am. J Addict 13 438 446 10.1080/10550490490512762 15764422 · DOI
  55. Slawecki CJ Thorsell AK Khoury AE Mathe AA Ehlers CL 2005 Increased CRF-like and NPY-like immunoreactivity in adult rats exposed to nicotine during adolescence: Relation to anxiety-like and depressive-like behavior Neuropeptides 39 369 377 10.1016/j.npep.2005.06.002 16038974 · DOI · Paper page
  56. Slotkin TA Card J Seidler FJ 2014 Nicotine administration in adolescence reprograms the subsequent response to nicotine treatment and withdrawal in adulthood: Sex-selective effects on cerebrocortical serotonergic function Brain Res Bull 102 1 8 10.1016/j.brainresbull.2014.01.004 24487013 PMC3972282 · DOI
  57. Slotkin TA Seidler FJ 2007 A unique role for striatal serotonergic systems in the withdrawal from adolescent nicotine administration Neurotoxicol Teratol, Exposures during adolescent development: are neurotoxic risks increased? 29 10 16 10.1016/j.ntt.2006.06.001 16919421 · DOI
  58. Slotkin TA Stadler A Skavicus S Seidler FJ 2016 Adolescents and adults differ in the immediate and long-term impact of nicotine administration and withdrawal on cardiac norepinephrine Brain Res Bull 122 71 75 10.1016/j.brainresbull.2016.03.006 26993795 PMC4818666 · DOI
  59. Spear LP 2000 The adolescent brain and age-related behavioral manifestations Neurosci. Biobehav Rev 24 417 463 10.1016/S0149-7634(00)00014-2 10817843 · DOI · Paper page
  60. Spijker S Dissection of rodent brain regions Li KW 2011 Neuroproteomics, Neuromethods Humana Press 13 26 10.1007/978-1-61779-111-6_2 · DOI
  61. Trauth JA Seidler FJ McCook EC Slotkin TA 1999 Adolescent nicotine exposure causes persistent upregulation of nicotinic cholinergic receptors in rat brain regions Brain Research 851 9 19 10.1016/S0006-8993(99)01994-0 10642823 · DOI · Paper page
  62. Vetencourt JFM Tiraboschi E Spolidoro M Castrén E Maffei L 2011 Serotonin triggers a transient epigenetic mechanism that reinstates adult visual cortex plasticity in rats Eur. J. Neurosci 33 49 57 10.1111/j.l460-9568.2010.07488.x 21156002 · DOI
  63. Wang J-W David DJ Monckton JE Battaglia F Hen R 2008 Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells J. Neurosci 28 1374 1384 10.1523/JNEUROSCI.3632-07.2008 18256257 PMC6671574 · DOI · Paper page
  64. Wang Y Neumann M Hansen K Hong SM Kim S Noble-Haeusslein LJ Liu J 2011 Fluoxetine increases hippocampal neurogenesis and induces epigenetic factors but does not improve functional recovery after traumatic brain injury J. Neurotrauma 28 259 268 10.1089/neu.2010.1648 21175261 PMC5206695 · DOI
  65. Wehner JM Keller JJ Keller AB Picciotto MR Paylor R Booker TK Beaudet A Heinemann SF Balogh SA 2004 Role of neuronal nicotinic receptors in the effects of nicotine and ethanol on contextual fear conditioning Neuroscience 129 11 24 10.1016/j.neuroscience.2004.07.016 15489024 · DOI
  66. Xiao L Kish VL Benders KM Wu Z-X 2016 Prenatal and early postnatal exposure to cigarette smoke decreases BDNF/TrkB signaling and increases abnormal behaviors later in life Int. J. Neuropsychopharmacology 19 pyv117 10.1093/ijnp/pyv117 PMC4886663 26503133 · DOI
  67. 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 951 280 292 10.1016/S0006-8993(02)03174-8 12270507 · DOI
  68. Yildirim E Connor DA Gould TJ 2015 ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice Behav. Pharmacol 26 241 248 10.1097/FBP.0000000000000111 25426579 PMC4459497 · DOI

Authors
Connor, D. A., & Gould, T. J.
Affiliations
Temple University (US)
Corresponding author
Gould, Thomas J.
ORCID
Gould, Thomas J.
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2017-10
Volume
125
Pages
272-283
ISSN
0028-3908 (ISSN-L)
DOI
10.1016/j.neuropharm.2017.07.033
PMC
PMC5757519
OpenAlex
W2739720415
Cited by
15
References
98
Citations by year
2026: 2 · 2024: 3 · 2023: 5 · 2022: 1 · 2019: 3 · 2018: 1
FWCI
0.81
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIDA/NIH (DA017949)
  • Penn State
  • Shibley Endowment
Topics
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
chronic nicotine exposure, adolescent nicotine exposure, fluoxetine, trace fear conditioning, hippocampus-dependent learning, brain-derived neurotrophic factor, dorsal hippocampus, ventral hippocampus, prefrontal cortex, anxiety, nicotine abstinence, adolescent brain development, learning deficits
MeSH terms
Aging, Animals, Anxiety, Conditioning, Psychological, Fear, Fluoxetine, Hippocampus, Learning Disabilities, Male, Mice, Inbred C57BL, Nicotine, Prefrontal Cortex, Nootropic Agents, Nicotinic Agonists, Brain-Derived Neurotrophic Factor, Substance-Related Disorders

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