Mucha R F, Fassos F F, Perl F M
Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Germany.
Drug Alcohol Depend. 1995 Jul;39(1):1-6. doi: 10.1016/0376-8716(95)01116-g.
Pentylenetetrazol (PTZ) and sodium valproate (VPA) produce acutely in the naive rat various behavioural effects resembling signs of opiate withdrawal in the morphine-treated subject. Suggestions in the literature that these substances may activate directly some of the neural consequences of opiate and drug withdrawal prompted us to look for and examine possible aversive effects of these substances at non-toxic doses. With a sensitive two-flavour, three-trial taste aversion procedure, relatively low doses of PTZ and VPA (5 and 160 mg/kg, respectively) do indeed have aversive effects. The maximum aversions were produced by 10 and 20 mg/kg PTZ and 320 mg/kg VPA and were equivalent to those of morphine withdrawal precipitated by 0.01-0.03 mg/kg naloxone in a morphine pellet-implanted animal. Moreover, the maximum aversions with PTZ and VPA were significantly higher than the maximum aversions seen with naloxone in the drug-naive animal under the same training conditions. Thus, the data from the present study confirmed the notion that low doses of PTZ and VPA in the naive animal may activate processes activated by drug withdrawal, including those important for the motivational effect of withdrawal. However, it was also pointed out that the lowest dose VPA producing aversion was higher than that found here to produce writhes and ataxia (80 mg/kg) but the same as that required for shaking (160 mg/kg), while the PTZ aversion was at a dose lower than that known to produce a PTZ cue. Implications were discussed for using withdrawal-like phenomena as a model in the non-treated organism of clinically-relevant withdrawal effects.
戊四氮（PTZ）和丙戊酸钠（VPA）在未接触过药物的大鼠中会急性产生各种行为效应，类似于吗啡处理过的动物出现的阿片类药物戒断症状。文献中提出这些物质可能直接激活阿片类药物和药物戒断的一些神经后果，这促使我们寻找并研究这些物质在无毒剂量下可能产生的厌恶效应。通过一种灵敏的双味、三次试验的味觉厌恶程序，相对低剂量的PTZ和VPA（分别为5和160mg/kg）确实具有厌恶效应。10和20mg/kg的PTZ以及320mg/kg的VPA产生了最大厌恶效应，其程度与在植入吗啡丸剂的动物中由0.01 - 0.03mg/kg纳洛酮诱发的吗啡戒断效应相当。此外，在相同训练条件下，PTZ和VPA产生的最大厌恶效应显著高于未接触过药物的动物中纳洛酮产生的最大厌恶效应。因此，本研究的数据证实了这样一种观点，即未接触过药物的动物中低剂量的PTZ和VPA可能激活由药物戒断激活的过程，包括那些对戒断动机效应重要的过程。然而，也有人指出，产生厌恶效应的最低剂量VPA高于此处发现的产生扭体和共济失调的剂量（80mg/kg），但与引起颤抖所需的剂量相同（160mg/kg），而PTZ产生厌恶效应的剂量低于已知产生PTZ提示的剂量。文中讨论了将类似戒断现象用作未处理生物体中临床相关戒断效应模型的意义。
