Endogenous adenosine-receptive systems do not mediate the discriminative stimulus properties of ethanol.

Alcohol and drug research Pub Date : 1987-01-01
R C Michaelis, A M Holohean, G A Hunter, F A Holloway
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Abstract

Adenosine is an endogenous neuromodulator with depressant effects on CNS neurons. Adenosine agonists produce biphasic effects on activity, decreases in operant response rate, and anticonvulsant effects. These effects are similar to some of the behavioral effects of ethanol. In addition, it has recently been shown that relative sensitivities to some of the behavioral effects of ethanol and purinergic drugs are similar in inbred strains of mice. These findings have prompted the speculation that ethanol's behavioral effects may be mediated by an agonist action on adenosine-receptive neurons. The present study provided a direct test of this hypothesis with respect to the discriminative stimulus properties of ethanol. In this study, neither the A1 receptor agonist N6-cyclohexyladenosine nor the A2 receptor agonist N6-ethylcarboxamide adenosine produced significant generalization to the ethanol stimulus. In addition, neither the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine nor the adenosine uptake inhibitor dipyridamole were able to enhance the level of ethanol-appropriate responding seen after a low dose of ethanol. Both caffeine and 8-phenyltheophylline partially but significantly antagonized the stimulus properties of ethanol. However, the doses required to achieve these effects were much higher than those needed to block adenosine receptors. These findings strongly suggest that the discriminative stimulus properties of ethanol are not mediated through an agonist action on adenosine-receptive neurons.

内源性腺苷接受系统不介导乙醇的鉴别刺激特性。
腺苷是一种内源性神经调节剂,对中枢神经系统神经元具有抑制作用。腺苷激动剂对活性产生双相作用,降低手术反应率和抗惊厥作用。这些影响类似于乙醇对行为的影响。此外,最近有研究表明,对乙醇和嘌呤能药物的某些行为影响的相对敏感性在近交系小鼠中是相似的。这些发现促使人们猜测乙醇的行为效应可能是通过对腺苷接受神经元的激动剂作用介导的。本研究就乙醇的判别刺激特性对这一假设进行了直接检验。在本研究中,A1受体激动剂n6 -环己基腺苷和A2受体激动剂n6 -乙基羧酰胺腺苷都没有对乙醇刺激产生明显的泛化作用。此外,腺苷脱氨酶抑制剂红-9-(2-羟基-3-壬基)-腺嘌呤和腺苷摄取抑制剂双嘧达莫都不能提高低剂量乙醇后的乙醇适宜反应水平。咖啡因和8-苯基茶碱均部分但显著地拮抗乙醇的刺激特性。然而,达到这些效果所需的剂量远远高于阻断腺苷受体所需的剂量。这些发现有力地表明,乙醇的鉴别刺激特性不是通过对腺苷接受神经元的激动剂作用介导的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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