title: Increased opioid dependence in a mouse model of panic disorder.
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 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.
authors.affiliation: Genes and Disease Program, Genomic Regulation Center-CRG, Barcelona Biomedical Research Park-PRBB and CIBER de Enfermedades Raras Barcelona, Catalonia, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Gallego
authors.forename: Patricia
authors.initials: P
authors.lastname: Murtra
authors.forename: Teresa
authors.initials: T
authors.lastname: Zamalloa
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Canals
authors.forename: Joseba
authors.initials: J
authors.lastname: Pineda
authors.forename: Alejandro
authors.initials: A
authors.lastname: Amador-Arjona
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Mara
authors.initials: M
authors.lastname: Dierssen