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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/31059

Title: Involvement of Noradrenergic Transmission in the PVN on CREB Activation, TORC1 Levels, and Pituitary-Adrenal Axis Activity during Morphine Withdrawal
Authors: Martín, Fátima
Núñez, Cristina
Marín Boscá, María Teresa
Laorden, María Luisa
Kovács, Krisztina J.
Milanés, M. Victoria
Issue Date: 2012
Abstract: Experimental and clinical findings have shown that administration of adrenoceptor antagonists alleviated different aspects of drug withdrawal and dependence. The present study tested the hypothesis that changes in CREB activation and phosphorylated TORC1 levels in the hypothalamic paraventricular nucleus (PVN) after naloxone-precipitated morphine withdrawal as well as the HPA axis activity arises from α1- and/or β-adrenoceptor activation. The effects of morphine dependence and withdrawal on CREB phosphorylation (pCREB), phosphorylated TORC1 (pTORC1), and HPA axis response were measured by Western-blot, immunohistochemistry and radioimmunoassay in rats pretreated with prazosin (α1-adrenoceptor antagonist) or propranolol (β-adrenoceptor antagonist). In addition, the effects of morphine withdrawal on MHPG (the main NA metabolite at the central nervous system) and NA content and turnover were evaluated by HPLC. We found an increase in MHPG and NA turnover in morphine-withdrawn rats, which were accompanied by increased pCREB immunoreactivity and plasma corticosterone concentrations. Levels of the inactive form of TORC1 (pTORC1) were decreased during withdrawal. Prazosin but not propranolol blocked the rise in pCREB level and the decrease in pTORC1 immunoreactivity. In addition, the HPA axis response to morphine withdrawal was attenuated in prazosin-pretreated rats. Present results suggest that, during acute morphine withdrawal, NA may control the HPA axis activity through CREB activation at the PVN level. We concluded that the combined increase in CREB phosphorylation and decrease in pTORC1 levels might represent, in part, two of the mechanisms of CREB activation at the PVN during morphine withdrawal.
Sponsorship: This work was supported by Ministerio de Ciencia e Innovación (SAF2009-07178 and SAF2010-17907), Red de Trastornos Adictivos (RTA; RD06/0001/1006) and Fundación Séneca (15405/PI/10), Agencia Regional de Ciencia y Tecnología, Región de Murcia.
Publisher: Public Library of Science (PLOS)
Keywords: Analysis of variance
Body weight
DNA transcription
Drug addiction
Morphine
Neurons
Opiates
Phosphorylation
URI: http://hdl.handle.net/10481/31059
ISSN: 1932-6203
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: Martín, F.; et al. Involvement of Noradrenergic Transmission in the PVN on CREB Activation, TORC1 Levels, and Pituitary-Adrenal Axis Activity during Morphine Withdrawal. Plos One, 7(2): e31119 (2012). [http://hdl.handle.net/10481/31059]
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