Can experimental paradigms and animal models be used to discover clinically effective medications for alcoholism?

被引:65
作者
Egli, M [1 ]
机构
[1] NIAAA, Div Neurosci & Behav, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA
关键词
D O I
10.1080/13556210500314550
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Evaluating medications in animal laboratory paradigms can reveal whether the compound is effective in an established alcoholism model, at clinically relevant doses and exposure conditions, when administered orally (or transdermally) and without serious limiting side effects. Positive outcomes constitute a possible discovery for relevance to alcoholism and, under favorable marketing conditions, encourage further development. Medication testing using animal models of alcoholism might also guide clinical testing by discriminating clinically effective front clinically ineffective compounds. This ability rests on whether there are tests or, more reasonably, batteries of tests having this discriminative ability. The present paper examines this possibility. Effects of naltrexone and acamprosate in animal paradigms which model behavioral aspects of alcoholism are reviewed and compared with the effects of compounds which have limited effects in alcoholics. It is not clear at present whether any single paradigm or combination of paradigms differentiates clinically effective from clinically limited compounds. Steps are suggested to improve the use of preclinical laboratory tests to predict which compounds are likely to be effective medications for reducing drinking and sustaining abstinence in human alcoholics.
引用
收藏
页码:309 / 319
页数:11
相关论文
共 119 条
[91]   Appetitive and consummatory behaviors in the control of ethanol consumption: A measure of ethanol seeking behavior [J].
Samson, HH ;
Slawecki, CJ ;
Sharpe, AL ;
Chappell, A .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1998, 22 (08) :1783-1787
[92]   Opposite effects of acute versus chronic naltrexone administration on ethanol-induced locomotion [J].
Sanchis-Segura, C ;
Pastor, R ;
Aragon, CMG .
BEHAVIOURAL BRAIN RESEARCH, 2004, 153 (01) :61-67
[93]   Effects of chronic ethanol exposure on oral self-administration of ethanol or saccharin by Wistar rats [J].
Schulteis, G ;
Hyytia, P ;
Heinrichs, SC ;
Koob, GF .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1996, 20 (01) :164-171
[94]   Effect of naloxone on appetitive and consummatory phases of ethanol self-administration [J].
Sharpe, AL ;
Samson, HH .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2001, 25 (07) :1006-1011
[95]   Effects of naltrexone and Ro 15-4513 on a multiple schedule of ethanol and Tang self-administration [J].
Shelton, KL ;
Grant, KA .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2001, 25 (11) :1576-1585
[96]   A DRUG DISCRIMINATION ANALYSIS OF ETHANOL-INDUCED BEHAVIORAL EXCITATION AND SEDATION - THE ROLE OF ENDOGENOUS OPIATE PATHWAYS [J].
SHIPPENBERG, TS ;
ALTSHULER, HL .
ALCOHOL, 1985, 2 (02) :197-201
[97]   Evidence about the use of naltrexone and for different ways of using it in the treatment of alcoholism [J].
Sinclair, JD .
ALCOHOL AND ALCOHOLISM, 2001, 36 (01) :2-10
[98]  
SINCLAIR JD, 1989, Patent No. 4882335
[99]   The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption [J].
Spanagel, R ;
Pendyala, G ;
Abarca, C ;
Zghoul, T ;
Sanchis-Segura, C ;
Magnone, MC ;
Lascorz, J ;
Depner, M ;
Holzberg, D ;
Soyka, M ;
Schreiber, S ;
Matsuda, F ;
Lathrop, M ;
Schumann, G ;
Albrecht, U .
NATURE MEDICINE, 2005, 11 (01) :35-42
[100]   Acamprosate and alcohol .3. Effects on alcohol discrimination in the rat [J].
Spanagel, R ;
Zieglgansberger, W ;
Hundt, W .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1996, 305 (1-3) :51-56