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Title: Increased opioid dependence in a mouse model of panic disorder
Author: Gallego, Xavier
Murtra, Patricia
Zamalloa, Teresa
Canals i Coll, Josep M.
Pineda, Joseba
Amador-Arjona, Alejandro
Maldonado, Rafael, 1961-
Dierssen, Mara
Keywords: Trastorns de pànic
Abús de substàncies
Rates (Animals de laboratori)
Animals transgènics
Panic disorders
Substance abuse
Rats as laboratory animals
Transgenic animals
Issue Date: 2010
Publisher: Frontiers Media
Abstract: 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 met5-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.
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It is part of: Frontiers in Behavioral Neuroscience, 2010, vol. 3
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ISSN: 1662-5153
Appears in Collections:Articles publicats en revistes (Biomedicina)

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