PMID- 25267343
OWN - NLM
STAT- MEDLINE
DCOM- 20160105
LR  - 20211021
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 40
IP  - 4
DP  - 2015 Mar
TI  - Chronic amitriptyline treatment attenuates nigrostriatal degeneration and 
      significantly alters trophic support in a rat model of parkinsonism.
PG  - 874-83
LID - 10.1038/npp.2014.262 [doi]
AB  - In addition to alleviating depression, long-term adaptive changes induced by 
      antidepressants may regulate neural plasticity in the diseased brain, providing 
      symptomatic and disease-modifying effects in Parkinson's disease. The present 
      study investigated whether chronic treatment with a frequently prescribed 
      tricyclic antidepressant was neuroprotective in a 6-hydroxydopamine (6-OHDA) rat 
      model of parkinsonism. In lesioned animals, chronic amitriptyline (AMI; 5 mg/kg) 
      treatment resulted in a significant sparing of tyrosine 
      hydroxylase-immunoreactive (THir) neurons in the substantia nigra pars compacta 
      (SNpc) compared with saline treatment. Additionally, striatal fibers were 
      preserved and functional motor deficits were attenuated. Although 6-OHDA lesions 
      did not induce anhedonia in our model, the dose of AMI utilized had 
      antidepressant activity as demonstrated by reduced immobility. Recent in vitro 
      and in vivo data provide evidence that trophic factors such as brain-derived 
      neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) 
      may be key mediators of the therapeutic response to antidepressants. Therefore, 
      we investigated whether AMI mediates changes in these specific trophic factors in 
      the intact and degenerating nigrostriatal system. Chronic AMI treatment mediates 
      an increase in nigral BDNF both before and during ongoing degeneration, 
      suggesting it may contribute to neuroprotection observed in vivo. However, over 
      time, AMI reduced BDNF levels in the striatum, indicating tricyclic therapy 
      differentially regulates trophic factors within the nigrostriatal system. 
      Combined, these results suggest that AMI treatment attenuates dopamine neuron 
      loss and elicits significant trophic changes relevant to dopamine neuron 
      survival.
FAU - Paumier, Katrina L
AU  - Paumier KL
AD  - Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
FAU - Sortwell, Caryl E
AU  - Sortwell CE
AD  - Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
FAU - Madhavan, Lalitha
AU  - Madhavan L
AD  - Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
FAU - Terpstra, Brian
AU  - Terpstra B
AD  - Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
FAU - Celano, Stephanie L
AU  - Celano SL
AD  - Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
FAU - Green, Joshua J
AU  - Green JJ
AD  - Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
FAU - Imus, Nastassja M
AU  - Imus NM
AD  - Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
FAU - Marckini, Nathan
AU  - Marckini N
AD  - Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
FAU - Daley, Brian
AU  - Daley B
AD  - Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
FAU - Steece-Collier, Kathy
AU  - Steece-Collier K
AD  - Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
FAU - Collier, Timothy J
AU  - Collier TJ
AD  - Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
LA  - eng
GR  - P50 NS058830/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140930
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Adrenergic Agents)
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 1806D8D52K (Amitriptyline)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - FST467XS7D (Saccharin)
SB  - IM
MH  - Adrenergic Agents/toxicity
MH  - Amitriptyline/*therapeutic use
MH  - Analgesics, Non-Narcotic/*therapeutic use
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Corpus Striatum/*pathology
MH  - Disease Models, Animal
MH  - Food Preferences
MH  - Gene Expression Regulation/drug effects
MH  - Hindlimb Suspension
MH  - Male
MH  - *Neurodegenerative Diseases/drug therapy/etiology/pathology
MH  - Oxidopamine/toxicity
MH  - Parkinsonian Disorders/chemically induced/*complications
MH  - Psychomotor Performance/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Saccharin/administration & dosage
MH  - Substantia Nigra/*pathology
MH  - Tyrosine 3-Monooxygenase/metabolism
PMC - PMC4330501
EDAT- 2014/10/01 06:00
MHDA- 2016/01/06 06:00
PMCR- 2016/03/01
CRDT- 2014/10/01 06:00
PHST- 2014/02/26 00:00 [received]
PHST- 2014/08/22 00:00 [revised]
PHST- 2014/09/16 00:00 [accepted]
PHST- 2014/10/01 06:00 [entrez]
PHST- 2014/10/01 06:00 [pubmed]
PHST- 2016/01/06 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - npp2014262 [pii]
AID - 10.1038/npp.2014.262 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2015 Mar;40(4):874-83. doi: 10.1038/npp.2014.262. Epub 
      2014 Sep 30.