DISCRIMINATIVE STIMULUS PROPERTIES OF 8-OH-DPAT - RELATIONSHIP TO AFFINITY FOR 5HT(1A) RECEPTORS

被引:45
作者
SANGER, DJ
SCHOEMAKER, H
机构
[1] Synthélabo Recherche (L.E.R.S.), Bagneux, F-92220
关键词
DRUG DISCRIMINATION; 5HT(1A) RECEPTORS; 8-OH-DPAT;
D O I
10.1007/BF02245290
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Previous studies have shown that discriminative stimulus control established with the 5HT1A receptor agonist, 8-OH-DPAT, generalises to other 5HT1A agonists and partial agonists but also to the alpha(2)-adrenoceptor antagonist, yohimbine. On the basis of these results it has been proposed that the 8-OH-DPAT cue may be produced by activity at more than one receptor. In the present study rats were trained to discriminate a dose of 8-OH-DPAT (0.05 mg/kg, SC) from saline. Substitution tests showed dose-dependent generalisation with the 5HT1A compounds, buspirone, ipsapirone, MDL 72832 and MDL 73005EF, the alpha(2)-adrenoceptor antagonists, yohimbine and idazoxan, and BMY 14802, which is usually described as a sigma ligand. The buspirone metabolite 1-pyrimidinyl piperazine (1-PP) which possesses mainly alpha(2)-adrenoceptor antagonist properties produced only partial generalisation which was not dose related. Receptor binding studies showed that all the compounds which substituted for 8-OH-DPAT displaced [H-3]-8-OH-DPAT binding to rat hippocampal membranes. Furthermore, there were statistically significant positive correlations between drug affinity for 5HT1A sites and their ED50 values for both substitution for 8-OH-DPAT and potency to decrease response rates. These results are consistent with the view that the 8-OH-DPAT cue, like the ability of the compounds tested to decrease rates of responding, is largely mediated by activity at 5HT1A receptors.
引用
收藏
页码:85 / 92
页数:8
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