Ujike H, Okumura K, Zushi Y, Akiyama K, Otsuki S
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Eur J Pharmacol. 1992 Feb 18;211(3):323-8. doi: 10.1016/0014-2999(92)90388-k.
Functional changes in sigma receptors were examined after behavioral sensitization induced by repeated methamphetamine treatment. Rats received either saline or 4 mg/kg methamphetamine for 14 days. (+)3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP), a sigma receptor agonist, was given as challenge after various periods of abstinence. (+)-3-PPP at doses greater than 6 mg/kg stimulated several forms of behavior in naive rats. (+)-3-PPP at 12 and 24 mg/kg produced more frequent rearing and more intense stereotyped sniffing and repetitive head movements in rats previously sensitized with methamphetamine than in saline-pretreated rats. The augmented response to (+)-3-PPP in methamphetamine-treated rats was maintained for at least one month. The augmented response to (+)-3-PPP was reversed by the combined administration of 100 mg/kg (+/-)-sulpiride, a D2 dopamine receptor antagonist, and 30 mg/kg BMY 14802, a sigma receptor antagonist. These results suggest that repeated methamphetamine treatment induces persistent supersensitivity in sigma receptors and that it may subsequently activate the dopamine system.
在反复给予甲基苯丙胺诱导行为敏化后，研究了西格玛受体的功能变化。大鼠连续14天接受生理盐水或4mg/kg甲基苯丙胺处理。在不同的戒断期后，给予西格玛受体激动剂（+）-3-（3-羟基苯基）-N-（1-丙基）哌啶（（+）-3-PPP）作为激发剂。剂量大于6mg/kg的（+）-3-PPP可刺激未致敏大鼠的多种行为。与生理盐水预处理的大鼠相比，12mg/kg和24mg/kg的（+）-3-PPP可使先前对甲基苯丙胺致敏的大鼠产生更频繁的竖毛行为、更强烈的刻板嗅探和重复性头部运动。甲基苯丙胺处理的大鼠对（+）-3-PPP的增强反应至少维持了一个月。100mg/kg的D2多巴胺受体拮抗剂（+/-）-舒必利和30mg/kg的西格玛受体拮抗剂BMY 14802联合给药可逆转对（+）-3-PPP的增强反应。这些结果表明，反复给予甲基苯丙胺可诱导西格玛受体持续超敏，随后可能激活多巴胺系统。
