Gene expression regulation following behavioral sensitization to cocaine in transgenic mice lacking the glucocorticoid receptor in the brain.
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.
Izawa
R
R
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.
Jaber
M
M
Deroche-Gamonet
V
V
Sillaber
I
I
Kellendonk
C
C
Le Moal
M
M
Tronche
F
F
Piazza
P V
PV
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics*; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004399:Dynorphins / Q000096:biosynthesis; D004745:Enkephalins / Q000096:biosynthesis; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D007608:Kainic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000096:biosynthesis / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics; D013373:Substance P / Q000096:biosynthesis; D009435:Synaptic Transmission / Q000187:drug effects; D000097806:GluK2 Kainate Receptor
D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D004399:Dynorphins; D004745:Enkephalins; D007608:Kainic Acid; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011965:Receptors, Glucocorticoid; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D013373:Substance P; D000097806:GluK2 Kainate Receptor