作为苯丙胺治疗后时间函数的双向线索的证据：对理解耐受性和戒断的启示。

Barrett Robert J, Caul William F, Smith Randy L

Veterans Administration Medical Center, Departments of Psychology and Pharmacology, Vanderbilt University, Research Service (151), 1310 24th Avenue South, Nashville, TN 37212-2637, USA.

Pharmacol Biochem Behav. 2004 Dec;79(4):761-71. doi: 10.1016/j.pbb.2004.10.005.

RATIONALE

Previous drug-discrimination studies have focused on characterizing the cue properties associated with amphetamine's (AMPH) primary effect. Results from recent experiments indicate that equally prominent cues are associated with AMPH withdrawal.

OBJECTIVES

The purpose of the present study was to investigate the extent to which AMPH-induced withdrawal cues, opposite to those associated with AMPH's primary effect are observed.

METHODS

Since dopamine (DA) has been implicated in mediating the AMPH cue, rats were trained to discriminate between 0.25 mg/kg AMPH, an indirect DA agonist, and 0.033 mg/kg haloperidol (HAL), a DA antagonist at the D2 receptor site. Training doses were chosen so that rats responded about equally on both levers when tested on saline (SAL) providing a behavioral baseline sensitive to assessing AMPH-related bidirectional changes in cue state. Following acquisition of the discrimination, rats were tested for choice of responding on the AMPH and HAL levers at intervals from 6 to 72 h following treatment with a single dose of 3.0 mg/AMPH. Also, in order to investigate the relationship between withdrawal and tolerance to AMPH's cue properties, AMPH dose-response curves were determined 24 h following treatment with SAL, 1.5 and 3.0 mg/kg AMPH.

RESULTS

At short intervals after treatment with 3.0 mg/kg AMPH, rats responded primarily on the AMPH lever followed by a shift to predominant responding on the HAL lever 16-30 h post-treatment, before returning to predrug levels. Treatment with 1.5 and 3.0 mg/kg AMPH produced parallel dose-response curve shifts to the right.

CONCLUSIONS

Following a single dose of AMPH, robust cues associated with AMPH withdrawal were observed that lasted approximately three times longer than the cues associated with the drug's primary effects. Furthermore, results from the tolerance tests indicate that tolerance reflects a baseline shift rather than a loss in drug efficacy.

原理

以往的药物辨别研究主要集中于表征与苯丙胺（AMPH）主要效应相关的线索特性。近期实验结果表明，同样显著的线索与AMPH戒断有关。

目的

本研究旨在探究与AMPH主要效应相反的AMPH诱导的戒断线索被观察到的程度。

方法

由于多巴胺（DA）被认为参与介导AMPH线索，大鼠被训练区分0.25mg/kg的AMPH（一种间接DA激动剂）和0.033mg/kg的氟哌啶醇（HAL，一种D2受体位点的DA拮抗剂）。选择训练剂量以便在以生理盐水（SAL）测试时大鼠在两个杠杆上的反应大致相同，从而提供一个对评估与AMPH相关的线索状态双向变化敏感的行为基线。在获得辨别能力后，在单次给予3.0mg/AMPH治疗后的6至72小时间隔内，测试大鼠在AMPH和HAL杠杆上的反应选择。此外，为了研究戒断与对AMPH线索特性耐受性之间的关系，在给予SAL、1.5和3.0mg/kg AMPH治疗24小时后测定AMPH剂量 - 反应曲线。