Suppressing effect of the cannabinoid CB1 receptor antagonist, SR 141716, on alcohol's motivational properties in alcohol-preferring rats

被引:45
作者
Colombo, G [1 ]
Vacca, G [1 ]
Serra, S [1 ]
Carai, MAM [1 ]
Gessa, GL [1 ]
机构
[1] Univ Cagliari, Bernard B Brodie Dept Neurosci, Sect Cagliari, CNR,Inst Neurosci, I-09126 Cagliari, Italy
关键词
cannabinoid CB1 receptor antagonist; SR; 141716; extinction responding for alcohol; Sardinian alcohol-preferring (sP); rat;
D O I
10.1016/j.ejphar.2004.07.069
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Administration of the cannabinoid CB, receptor antagonist, SR 141716 [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide], has been reported to reduce alcohol intake and alcohol self-administration in different models of excessive alcohol consumption, including the selectively bred Sardinian alcohol-preferring (sP) rats. The present study investigated whether SR 141716 was also capable of decreasing, in this rat line, alcohol's motivational properties. Extinction responding for alcohol, defined as the maximal number of lever responses reached in the absence of alcohol in rats trained to lever-press for alcohol, was used as index of alcohol's motivational properties. Rats were initially trained to lever-press for oral alcohol (15%, v/v) under a fixed ratio (FR) schedule of FR4. Once self-administration behavior was established, extinction sessions were conducted. SR 141716 (0, 0.3, 1 and 3 mg/kg; i.p.) was acutely administered before extinction sessions. In order to assess the specificity of SR 141716 action on extinction responding for alcohol, a separate group of sP rats was trained to lever-press for a 3% (w/v) sucrose solution under an FR4 schedule. SR 141716 administration produced a dose-dependent, virtually complete suppression of extinction responding for alcohol. In contrast, extinction responding for sucrose was not significantly altered by treatment with SR 141716. Further to the consummatory aspects, these results also extend the suppressing effect of SR 141716 to the appetitive aspects of alcohol drinking behavior in sP rats. The results also implicate the cannabinoid CB, receptor in the neural substrate mediating alcohol's motivational properties in this rat line. (C) 2004 Elsevier B.V All rights reserved.
引用
收藏
页码:119 / 123
页数:5
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