Memory enhancement mediated by the steroid sulfatase inhibitor (p-O-sulfamoyl)-N-tetradecanoyl tyramine

被引:22
作者
Li, PK
Rhodes, ME
Burke, AM
Johnson, DA
机构
[1] DUQUESNE UNIV,GRAD SCH PHARMACEUT SCI,DIV PHARMACOL TOXICOL,PITTSBURGH,PA 15282
[2] DUQUESNE UNIV,GRAD SCH PHARMACEUT SCI,DIV MED CHEM,PITTSBURGH,PA 15282
关键词
DHEAS; steroid sulfatase inhibitors; p-O-(sulfamoyl)-N-tetradecanoyl tyramine; DU-14; memory; passive avoidance;
D O I
10.1016/S0024-3205(96)00621-2
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The intent of this study was to determine whether altering the metabolism of neurosteroids via blockade of the enzyme, steroid sulfatase, could enhance memory retention in rats. The steroid sulfatase inhibitor p-O-(sulfamoyl)-N-tetradecanoyl tyramine (DU-14) was administered alone and in combination with the neurosteroid dehydroepiandrosterone sulfate (DHEAS) to rats which were then tested for the reversal of scopolamine-induced amnesia. A single 30 mg/kg IP dose of DU-14 produced a significant inhibition of steroid sulfatase activity in both brain (14.8%), and liver (85.2%) tissues, 24 hours following administration. In a passive avoidance test, DU-14 enhanced the reversal of amnesia by DHEAS. These results suggest that steroid sulfatase inhibition can potentiate the memory enhancing properties of DHEAS.
引用
收藏
页码:PL45 / PL51
页数:7
相关论文
共 16 条
  • [1] ALLEN CN, 1981, SOC NEUR ABSTR, V7, P515
  • [2] RECEPTOR-BINDING AND ELECTROPHYSIOLOGICAL EFFECTS OF DEHYDROEPIANDROSTERONE SULFATE, AN ANTAGONIST OF THE GABA(A) RECEPTOR
    DEMIRGOREN, S
    MAJEWSKA, MD
    SPIVAK, CE
    LONDON, ED
    [J]. NEUROSCIENCE, 1991, 45 (01) : 127 - 135
  • [3] GABA-ACTIVE STEROIDS - ENDOGENOUS MODULATORS OF GABA-GATED CHLORIDE-ION CONDUCTANCE
    DEUTSCH, SI
    MASTROPAOLO, J
    HITRI, A
    [J]. CLINICAL NEUROPHARMACOLOGY, 1992, 15 (05) : 352 - 364
  • [4] DEHYDROEPIANDROSTERONE SULFATE IMPROVES MEMORY IN AGING MICE
    FLOOD, JF
    ROBERTS, E
    [J]. BRAIN RESEARCH, 1988, 448 (01) : 178 - 181
  • [5] DEHYDROEPIANDROSTERONE AND ITS SULFATE ENHANCE MEMORY RETENTION IN MICE
    FLOOD, JF
    SMITH, GE
    ROBERTS, E
    [J]. BRAIN RESEARCH, 1988, 447 (02) : 269 - 278
  • [6] MEMORY-ENHANCING EFFECTS IN MALE-MICE OF PREGNENOLONE AND STEROIDS METABOLICALLY DERIVED FROM IT
    FLOOD, JF
    MORLEY, JE
    ROBERTS, E
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (05) : 1567 - 1571
  • [7] SEPTOHIPPOCAMPAL DISINHIBITION
    KRNJEVIC, K
    ROPERT, N
    CASULLO, J
    [J]. BRAIN RESEARCH, 1988, 438 (1-2) : 182 - 192
  • [8] REVERSAL OF SCOPOLAMINE-INDUCED AMNESIA IN RATS BY THE STEROID SULFATASE INHIBITOR ESTRONE-3-O-SULFAMATE
    LI, PK
    RHODES, ME
    JAGANNATHAN, S
    JOHNSON, DA
    [J]. COGNITIVE BRAIN RESEARCH, 1995, 2 (04): : 251 - 254
  • [9] NEUROSTEROIDS - ENDOGENOUS BIMODAL MODULATORS OF THE GABA-A RECEPTOR - MECHANISM OF ACTION AND PHYSIOLOGICAL SIGNIFICANCE
    MAJEWSKA, MD
    [J]. PROGRESS IN NEUROBIOLOGY, 1992, 38 (04) : 379 - 395
  • [10] THE NEUROSTEROID DEHYDROEPIANDROSTERONE SULFATE IS AN ALLOSTERIC ANTAGONIST OF THE GABA-A RECEPTOR
    MAJEWSKA, MD
    DEMIRGOREN, S
    SPIVAK, CE
    LONDON, ED
    [J]. BRAIN RESEARCH, 1990, 526 (01) : 143 - 146