期刊
NEUROPHARMACOLOGY
卷 57, 期 1, 页码 8-17出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2009.03.014
关键词
Morphine; Self-administration; Lewis and Fischer 344; Dopamine; Autoradiography; Extinction
资金
- Ministerio de Educacion y Ciencia [SAF2004-08148, SAF2007-064890]
- Ministerio de Sanidad y Consumo [RD06/00170029]
- Plan Nacional sobre [2004-2007, 2008-2010]
- Direccion General de Investigacion de la Comunidad de Madrid [S-SAL/0261/2006]
- Consorcio I+D CANNAB-CM)
- LINED
The Lewis (LEW) and Fischer 344 (F344) rat strains have been used as a model to study genetic vulnerability to drug addiction and they differ in their dopaminergic systems. We have studied the variation in the D1-like and D2-like receptors in distinct brain regions of LEW and F344 rats that self-administered morphine (1 mg/kg) for 15 days and also after different extinction periods (3, 7 and 15 days). Under basal conditions, binding to D1-like receptors in the olfactory tubercle and substantia nigra, and to D2-like receptors in the Pyriform cortex and hippocampal-CA1 was lower in LEW rats than in F344 rats. Conversely, the LEW rats exhibited stronger D2-like binding in the caudate-putamen. In most brain regions there was a decrease in D1-like binding in LEW rats after self-administration while the F344 animals displayed an increment. Additionally, D2 receptors of LEW rats were down-regulated after self-administration in the caudate-putamen and in the nucleus accumbens (shell and core divisions). Binding to D1-like receptors increased in both strains in the early phases of extinction, while in the later stages a differential regulation was observed between both strains. During the early phases of extinction only F344 rats showed alterations in D2-like receptor binding, however in the latter phases a specific modulation occurred in both strains. These differences in basal D1-like and D2-like receptor binding, and their differential modulation after self-administration and during extinction, may be reflected in the greater vulnerability to opiate addiction shown by LEW strain. (C) 2009 Elsevier Ltd. All rights reserved.
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