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High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation.

Abstract A wide variety of antidepressants act as noncompetitive antagonists of nicotinic acetylcholine receptors (nAChRs), but the relationship between this antagonism and the therapeutic effects of antidepressants is unknown.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title biological psychiatry
Publication Year Start
%A Caldarone, Barbara J.; Harrist, Alexia; Cleary, Muriel A.; Beech, Robert D.; King, Sarah L.; Picciotto, Marina R.
%T High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation.
%J Biological psychiatry, vol. 56, no. 9, pp. 657-664
%D 11/2004
%V 56
%N 9
%M eng
%B A wide variety of antidepressants act as noncompetitive antagonists of nicotinic acetylcholine receptors (nAChRs), but the relationship between this antagonism and the therapeutic effects of antidepressants is unknown.
%K Amitriptyline, Analysis of Variance, Animals, Antidepressive Agents, Tricyclic, Behavior, Animal, Bromodeoxyuridine, Cell Count, Cell Proliferation, Dose-Response Relationship, Drug, Drosophila Proteins, Drug Interactions, Helplessness, Learned, Hindlimb Suspension, Hippocampus, Immunohistochemistry, Mecamylamine, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons, Nicotinic Antagonists, Nortriptyline, Receptors, Nicotinic, Swimming
%P 657
%L 664
%Y 10.1016/j.biopsych.2004.08.010
%W PHY
%G AUTHOR
%R 2004.......56..657C

@Article{Caldarone2004,
author="Caldarone, Barbara J.
and Harrist, Alexia
and Cleary, Muriel A.
and Beech, Robert D.
and King, Sarah L.
and Picciotto, Marina R.",
title="High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation.",
journal="Biological psychiatry",
year="2004",
month="Nov",
day="01",
volume="56",
number="9",
pages="657--664",
keywords="Amitriptyline",
keywords="Analysis of Variance",
keywords="Animals",
keywords="Antidepressive Agents, Tricyclic",
keywords="Behavior, Animal",
keywords="Bromodeoxyuridine",
keywords="Cell Count",
keywords="Cell Proliferation",
keywords="Dose-Response Relationship, Drug",
keywords="Drosophila Proteins",
keywords="Drug Interactions",
keywords="Helplessness, Learned",
keywords="Hindlimb Suspension",
keywords="Hippocampus",
keywords="Immunohistochemistry",
keywords="Mecamylamine",
keywords="Mice",
keywords="Mice, Inbred C57BL",
keywords="Mice, Knockout",
keywords="Neurons",
keywords="Nicotinic Antagonists",
keywords="Nortriptyline",
keywords="Receptors, Nicotinic",
keywords="Swimming",
abstract="A wide variety of antidepressants act as noncompetitive antagonists of nicotinic acetylcholine receptors (nAChRs), but the relationship between this antagonism and the therapeutic effects of antidepressants is unknown.",
issn="0006-3223",
doi="10.1016/j.biopsych.2004.08.010",
url="http://www.ncbi.nlm.nih.gov/pubmed/15522249",
language="eng"
}

%0 Journal Article
%T High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation.
%A Caldarone, Barbara J.
%A Harrist, Alexia
%A Cleary, Muriel A.
%A Beech, Robert D.
%A King, Sarah L.
%A Picciotto, Marina R.
%J Biological psychiatry
%D 2004
%8 Nov 01
%V 56
%N 9
%@ 0006-3223
%G eng
%F Caldarone2004
%X A wide variety of antidepressants act as noncompetitive antagonists of nicotinic acetylcholine receptors (nAChRs), but the relationship between this antagonism and the therapeutic effects of antidepressants is unknown.
%K Amitriptyline
%K Analysis of Variance
%K Animals
%K Antidepressive Agents, Tricyclic
%K Behavior, Animal
%K Bromodeoxyuridine
%K Cell Count
%K Cell Proliferation
%K Dose-Response Relationship, Drug
%K Drosophila Proteins
%K Drug Interactions
%K Helplessness, Learned
%K Hindlimb Suspension
%K Hippocampus
%K Immunohistochemistry
%K Mecamylamine
%K Mice
%K Mice, Inbred C57BL
%K Mice, Knockout
%K Neurons
%K Nicotinic Antagonists
%K Nortriptyline
%K Receptors, Nicotinic
%K Swimming
%U http://dx.doi.org/10.1016/j.biopsych.2004.08.010
%U http://www.ncbi.nlm.nih.gov/pubmed/15522249
%P 657-664

PT Journal
AU Caldarone, BJ
   Harrist, A
   Cleary, MA
   Beech, RD
   King, SL
   Picciotto, MR
TI High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation.
SO Biological psychiatry
JI Biol. Psychiatry
PD Nov
PY 2004
BP 657
EP 664
VL 56
IS 9
DI 10.1016/j.biopsych.2004.08.010
LA eng
DE Amitriptyline; Analysis of Variance; Animals; Antidepressive Agents, Tricyclic; Behavior, Animal; Bromodeoxyuridine; Cell Count; Cell Proliferation; Dose-Response Relationship, Drug; Drosophila Proteins; Drug Interactions; Helplessness, Learned; Hindlimb Suspension; Hippocampus; Immunohistochemistry; Mecamylamine; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons; Nicotinic Antagonists; Nortriptyline; Receptors, Nicotinic; Swimming
AB A wide variety of antidepressants act as noncompetitive antagonists of nicotinic acetylcholine receptors (nAChRs), but the relationship between this antagonism and the therapeutic effects of antidepressants is unknown.
ER

PMID- 15522249
OWN - NLM
STAT- MEDLINE
DA  - 20041103
DCOM- 20050131
LR  - 20131121
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 56
IP  - 9
DP  - 2004 Nov 1
TI  - High-affinity nicotinic acetylcholine receptors are required for antidepressant
      effects of amitriptyline on behavior and hippocampal cell proliferation.
PG  - 657-64
AB  - BACKGROUND: A wide variety of antidepressants act as noncompetitive antagonists
      of nicotinic acetylcholine receptors (nAChRs), but the relationship between this 
      antagonism and the therapeutic effects of antidepressants is unknown. METHODS:
      Antidepressant properties of the noncompetitive nAChR antagonist mecamylamine in 
      the forced swim test were tested alone and in combination with the tricyclic
      antidepressant amitriptyline. Mice lacking high-affinity nAChRs were tested in
      three behavioral models to determine whether these receptors are required for
      behavioral effects of amitriptyline in common models of antidepressant action.
      Finally, the brains of wild-type and knockout animals treated with amitriptyline 
      were examined to determine whether high-affinity nAChRs are required for
      antidepressant-induced increases in hippocampal cell proliferation. RESULTS:
      Inhibition of nAChRs by mecamylamine had antidepressant-like effects in the
      forced swim test and potentiated the antidepressant activity of amitriptyline
      when the two drugs were used in combination. Mice lacking high-affinity nAChRs
      showed no behavioral response to amitriptyline. Finally, after chronic treatment 
      with amitriptyline, nAChR knockout mice did not show the increase in hippocampal 
      cell proliferation seen in wild-type mice. CONCLUSIONS: These data support the
      hypothesis that antagonism of nAChRs is an essential component of the therapeutic
      action of antidepressants.
FAU - Caldarone, Barbara J
AU  - Caldarone BJ
AD  - Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New
      Haven, CT 06508, USA.
FAU - Harrist, Alexia
AU  - Harrist A
FAU - Cleary, Muriel A
AU  - Cleary MA
FAU - Beech, Robert D
AU  - Beech RD
FAU - King, Sarah L
AU  - King SL
FAU - Picciotto, Marina R
AU  - Picciotto MR
LA  - eng
GR  - DA00167/DA/NIDA NIH HHS/United States
GR  - DA00436/DA/NIDA NIH HHS/United States
GR  - DA10455/DA/NIDA NIH HHS/United States
GR  - DA13334/DA/NIDA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Nicotinic Antagonists)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (nicotinic acetylcholine receptor alpha-subunits, Drosophila)
RN  - 1806D8D52K (Amitriptyline)
RN  - 6EE945D3OK (Mecamylamine)
RN  - BL03SY4LXB (Nortriptyline)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Amitriptyline/*administration & dosage/blood
MH  - Analysis of Variance
MH  - Animals
MH  - Antidepressive Agents, Tricyclic/*administration & dosage/blood
MH  - Behavior, Animal/*drug effects
MH  - Bromodeoxyuridine/metabolism
MH  - Cell Count
MH  - Cell Proliferation/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drosophila Proteins
MH  - Drug Interactions
MH  - Helplessness, Learned
MH  - Hindlimb Suspension/methods
MH  - Hippocampus/*cytology
MH  - Immunohistochemistry/methods
MH  - Mecamylamine/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons/cytology/*drug effects
MH  - Nicotinic Antagonists/pharmacology
MH  - Nortriptyline/blood/pharmacology
MH  - Receptors, Nicotinic/deficiency/*physiology
MH  - Swimming/physiology
EDAT- 2004/11/04 09:00
MHDA- 2005/02/03 09:00
CRDT- 2004/11/04 09:00
PHST- 2004/04/26 [received]
PHST- 2004/08/12 [revised]
PHST- 2004/08/19 [accepted]
AID - S0006-3223(04)00896-0 [pii]
AID - 10.1016/j.biopsych.2004.08.010 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2004 Nov 1;56(9):657-64.
TY  - JOUR
AU  - Caldarone, Barbara J.
AU  - Harrist, Alexia
AU  - Cleary, Muriel A.
AU  - Beech, Robert D.
AU  - King, Sarah L.
AU  - Picciotto, Marina R.
PY  - 2004/Nov/01
TI  - High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation.
T2  - Biol. Psychiatry
JO  - Biological psychiatry
SP  - 657
EP  - 664
VL  - 56
IS  - 9
KW  - Amitriptyline
KW  - Analysis of Variance
KW  - Animals
KW  - Antidepressive Agents, Tricyclic
KW  - Behavior, Animal
KW  - Bromodeoxyuridine
KW  - Cell Count
KW  - Cell Proliferation
KW  - Dose-Response Relationship, Drug
KW  - Drosophila Proteins
KW  - Drug Interactions
KW  - Helplessness, Learned
KW  - Hindlimb Suspension
KW  - Hippocampus
KW  - Immunohistochemistry
KW  - Mecamylamine
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - Neurons
KW  - Nicotinic Antagonists
KW  - Nortriptyline
KW  - Receptors, Nicotinic
KW  - Swimming
N2  - A wide variety of antidepressants act as noncompetitive antagonists of nicotinic acetylcholine receptors (nAChRs), but the relationship between this antagonism and the therapeutic effects of antidepressants is unknown.
SN  - 0006-3223
UR  - http://dx.doi.org/10.1016/j.biopsych.2004.08.010
UR  - http://www.ncbi.nlm.nih.gov/pubmed/15522249
ID  - Caldarone2004
ER  - 
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