Department of Psychology and Centre for Neuroscience, University of Otago, Dunedin, New Zealand.
J Psychopharmacol. 1992 Jan;6(1):88-94. doi: 10.1177/026988119200600116.
The ability of the opiate antagonist, naloxone, to block the anti-conflict effects of the benzodiazepines suggests endogenous opioid involvement in the mechanism of action of these drugs. However naloxone's ability to attenuate the effects of the benzodiazepines in animal conflict paradigms appears to be schedule specific. It is effective in acquisition of a differential reinforcement of low rates of response (DRL) schedule but not in acquisition of a non-reward successive discrimination schedule. We tested the effects of naloxone and chlordiazepoxide on acquisition of DRL and on acquisition of a version of the same schedule (signalled DRL) which was like successive discrimination in having an explicit visual signal of non-reward. Chlordiazepoxide (5 mg/kg i.p.) impaired DRL responding by increasing burst responding and premature responding close to the criterion interval. Naloxone (3 mg/kg i.p.) alone decreased burst and premature responding, it also blocked the effects of chlordiazepoxide. The signalled DRL schedule produced essentially similar drug effects. Clearly the critical schedule parameter determining whether naloxone will attenuate the anxiolytic actions of the benzodiazepines is not the presence or absence of an explicit signal of conflict.
阿片拮抗剂纳洛酮能够阻断苯二氮䓬类药物的抗冲突作用，这表明内源性阿片参与了这些药物的作用机制。然而，纳洛酮在动物冲突范式中减弱苯二氮䓬类药物的作用似乎具有特定的时间表。它在获得差异强化低反应率（DRL）时间表的过程中是有效的，但在获得非奖励连续区分时间表的过程中则不是。我们测试了纳洛酮和地西泮对 DRL 获得的影响，以及对同一时间表的一个版本（信号 DRL）的影响，该版本在没有奖励时具有明确的视觉信号，类似于连续区分。地西泮（5 毫克/千克腹腔注射）通过增加接近标准间隔的爆发反应和过早反应来损害 DRL 反应。纳洛酮（3 毫克/千克腹腔注射）单独降低了爆发和过早反应，它还阻断了地西泮的作用。信号 DRL 时间表产生了基本相似的药物作用。显然，决定纳洛酮是否会减弱苯二氮䓬类药物的抗焦虑作用的关键时间表参数不是冲突的存在与否。
