Effects of acute "binge" cocaine on preprodynorphin, preproenkephalin, proopiomelanocortin, and corticotropin-releasing hormone receptor mRNA levels in the striatum and hypothalamic-pituitary-adrenal axis of mu-opioid receptor knockout mice

被引:33
作者
Zhou, Y
Spangler, R
Schlussman, SD
Yuferov, VP
Sora, I
Ho, A
Uhl, GR
Kreek, MJ
机构
[1] Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10021 USA
[2] NIDA, Intramural Res Program, Mol Neurol Branch, Baltimore, MD 21224 USA
[3] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA
[4] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21224 USA
关键词
corticosterone; RNA solution hybridization;
D O I
10.1002/syn.10101
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Cocaine administration increases activity at dopamine receptors, increases preprodynorphin (ppDyn) gene expression in the caudate-putamen (CPu), and activates the stress responsive hypothalamic-pituitary-adrenal (HPA) axis. To examine the hypothesis that mu-opioid receptors (MOR) may play roles in these cocaine effects, we tested the effects of acute "binge" pattern cocaine administration in mice with targeted disruption of the MOR gene. Wild-type (+/+) and homozygous MOR-deficient (-/-) mice received three injections of 15 mg/kg cocaine at 1-h intervals. Mice were sacrificed 30 min after the last injection and mRNAs for ppDyn and preproenkephalin (ppEnk) in the CPu and nucleus accumbens (NAc), and for type I corticotropin-releasing hormone receptor (CRH1 receptor) and proopiomelanocortin (POMC) in the hypothalamus and pituitary, were measured by solution hybridization RNase protection assays. Cocaine elevated ppDyn mRNA in the CPu, but not NAc, of both the MOR -/- and wild-type mice. ppEnk mRNA in the CPu, but not NAc, was lower in MOR -/- mice than in wild-type mice following cocaine administration. Hypothalamic CRH, receptor and POMC mRNAs were expressed at similar levels in untreated and in cocaine-treated mice of each genotype. However, there were lower basal levels of CRH, receptor mRNA in the anterior pituitary of the MOR -/- mice than in wild-type mice and the MOR -/- mice failed to show the cocaine-induced decreases in CRH, receptor mRNA found in the wild-type mice. Cocaine activated the HPA axis similarly in MOR -/- and wild-type mice, as reflected in similar increases in plasma corticosterone levels in both genotypes. These results support a specific role for MORs in acute cocaine effects on striatal ppEnk gene expression and fail to support critical roles for these receptors in acute cocaine's effects on either ppDyn gene expression or HPA activation. MOR -/- mice are useful models for studying cocaine effects on ppEnk gene expression that could aid interpretation of the similar postmortem phenomena found in human cocaine addicts. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:220 / 229
页数:10
相关论文
共 68 条
[1]   NALOXONE ATTENUATION OF THE EFFECT OF COCAINE ON REWARDING BRAIN-STIMULATION [J].
BAIN, GT ;
KORNETSKY, C .
LIFE SCIENCES, 1987, 40 (11) :1119-1125
[2]   CHANGES IN DOPAMINE RECEPTORS IN MOUSE STRIATUM FOLLOWING MORPHINE TREATMENTS [J].
BAUME, SDL ;
PATEY, G ;
MARCAIS, H ;
PROTAIS, P ;
COSTENTIN, J ;
SCHWARTZ, JC .
LIFE SCIENCES, 1979, 24 (25) :2333-2342
[3]   Morphine self-administration in μ-opioid receptor-deficient mice [J].
Becker, A ;
Grecksch, G ;
Brödemann, R ;
Kraus, J ;
Peters, B ;
Schroeder, H ;
Thiemann, V ;
Loh, HH ;
Höllt, V .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2000, 361 (06) :584-589
[5]   Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5 [J].
Bibb, JA ;
Chen, JS ;
Taylor, JR ;
Svenningsson, P ;
Nishi, A ;
Snyder, GL ;
Yan, Z ;
Sagawa, ZK ;
Ouimet, CC ;
Nairn, AC ;
Nestler, EJ ;
Greengard, P .
NATURE, 2001, 410 (6826) :376-380
[6]  
BOROWSKY B, 1991, J PHARMACOL EXP THER, V256, P204
[7]   QUANTITATION OF PREPROENKEPHALIN MESSENGER-RNA LEVELS IN BRAIN-REGIONS FROM MALE FISCHER RATS FOLLOWING CHRONIC COCAINE TREATMENT USING A RECENTLY DEVELOPED SOLUTION HYBRIDIZATION ASSAY [J].
BRANCH, AD ;
UNTERWALD, EM ;
LEE, SE ;
KREEK, MJ .
MOLECULAR BRAIN RESEARCH, 1992, 14 (03) :231-238
[8]  
CARROLL ME, 1986, J PHARMACOL EXP THER, V238, P1
[9]   MORPHINE AND DELTA-OPIATE AGONISTS LOCALLY STIMULATE INVIVO DOPAMINE RELEASE IN CAT CAUDATE-NUCLEUS [J].
CHESSELET, MF ;
CHERAMY, A ;
REISINE, TD ;
GLOWINSKI, J .
NATURE, 1981, 291 (5813) :320-322
[10]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159