Gene expression regulation following behavioral sensitization to cocaine in transgenic mice lacking the glucocorticoid receptor in the brain.
Neuroscience. 2006-01-01; 137(3): 915-924
Lire sur PubMed
1. Neuroscience. 2006 Feb;137(3):915-24. Epub 2005 Dec 2.
Gene expression regulation following behavioral sensitization to cocaine in
transgenic mice lacking the glucocorticoid receptor in the brain.
Izawa R(1), Jaber M, Deroche-Gamonet V, Sillaber I, Kellendonk C, Le Moal M,
Tronche F, Piazza PV.
(1)Institut National de la Santé et de la Recherche Scientifique U588,
Laboratoire de Psychobiologie des Comportements Adaptatifs, Domaine de Carreire,
rue Camille St Saëns, 33077 Bordeaux Cedex, France.
Several findings suggest that glucocorticoid hormones influence the propensity of
an individual to develop cocaine abuse. These hormones activate two related
transcription factors, the glucocorticoid receptor and the mineralocorticoid
receptor. We have shown previously that mice carrying a mutation of the
glucocorticoid receptor gene specifically in neural cells, glucocorticoid
receptor knock-out in the brain, show a dramatic decrease in cocaine-induced
self-administration and no behavioral sensitization to this drug, two
experimental procedures considered relevant models of addiction. Here, we
investigated in glucocorticoid receptor knock-out in the brain mice the
consequences of this mutation at the level of the expression of neuropeptide,
dopamine receptor and glutamate receptor subunit mRNAs. We quantified mRNA levels
in the cortex, striatum and accumbens under basal conditions and following acute
or repeated cocaine treatments. Our results show that, under basal conditions,
neuropeptide (substance P, dynorphin) and dopamine receptor (D1, D2) mRNAs were
decreased in glucocorticoid receptor knock-out in the brain mice in the dorsal
striatum but not in the accumbens. However, cocaine-induced changes in the levels
of these mRNAs were not modified in glucocorticoid receptor knock-out in the
brain mice. In contrast, mutant mice showed altered response in mRNA levels of
N-methyl-D-aspartate, GLUR5 and GLUR6 glutamate receptor subunits as well as of
enkephalin following cocaine administration. These modifications may be
associated to decrease of behavioral effects of cocaine observed in
glucocorticoid receptor knock-out in the brain mice.
PMID: 16326019 [Indexed for MEDLINE]