Document Detail

Increased opioid dependence in a mouse model of panic disorder.
MedLine Citation:
PMID:  20204153     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Panic disorder is a highly prevalent neuropsychiatric disorder that shows co-occurrence with substance abuse. Here, we demonstrate that TrkC, the high-affinity receptor for neurotrophin-3, is a key molecule involved in panic disorder and opiate dependence, using a transgenic mouse model (TgNTRK3). Constitutive TrkC overexpression in TgNTRK3 mice dramatically alters spontaneous firing rates of locus coeruleus (LC) neurons and the response of the noradrenergic system to chronic opiate exposure, possibly related to the altered regulation of neurotrophic peptides observed. Notably, TgNTRK3 LC neurons showed an increased firing rate in saline-treated conditions and profound abnormalities in their response to met(5)-enkephalin. Behaviorally, chronic morphine administration induced a significantly increased withdrawal syndrome in TgNTRK3 mice. In conclusion, we show here that the NT-3/TrkC system is an important regulator of neuronal firing in LC and could contribute to the adaptations of the noradrenergic system in response to chronic opiate exposure. Moreover, our results indicate that TrkC is involved in the molecular and cellular changes in noradrenergic neurons underlying both panic attacks and opiate dependence and support a functional endogenous opioid deficit in panic disorder patients.
Xavier Gallego; Patricia Murtra; Teresa Zamalloa; Josep Maria Canals; Joseba Pineda; Alejandro Amador-Arjona; Rafael Maldonado; Mara Dierssen
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Publication Detail:
Type:  Journal Article     Date:  2010-02-22
Journal Detail:
Title:  Frontiers in behavioral neuroscience     Volume:  3     ISSN:  1662-5153     ISO Abbreviation:  Front Behav Neurosci     Publication Date:  2010  
Date Detail:
Created Date:  2010-03-05     Completed Date:  2011-07-14     Revised Date:  2013-08-13    
Medline Journal Info:
Nlm Unique ID:  101477952     Medline TA:  Front Behav Neurosci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  60     Citation Subset:  -    
Genes and Disease Program, Genomic Regulation Center-CRG, Barcelona Biomedical Research Park-PRBB and CIBER de Enfermedades Raras Barcelona, Catalonia, Spain.
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