Ujike H, Tsuchida K, Akiyama K, Otsuki S
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Life Sci. 1992;51(6):PL31-6. doi: 10.1016/0024-3205(92)90415-l.
We investigated the role of sigma receptors in the expression of behavioral sensitization induced by cocaine. Rats received intraperitoneal injections of either 20 mg/kg cocaine or saline once daily for 14 consecutive days. Cocaine-treated rats became sensitized. After a 5-day abstinence period, a challenge dose of (+)-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine ((+)-3-PPP), a sigma receptor agonist, was administered. (+)-3-PPP at doses of 12 and 24 mg/kg induced significantly more frequent rearing and more potent stereotypy consisting of repetitive head movement and sniffing in cocaine-sensitized rats than in saline-pretreated rats. These enhanced responses to (+)-3-PPP lasted for at least a month. The enhanced responses to (+)-3-PPP were attenuated by 30 mg/kg BMY 14802, a putative sigma antagonist, and also attenuated by 100 mg/kg (+/-)-sulpiride, a D2 dopamine antagonist. These findings show that repeated administration of cocaine produces lasting supersensitivity of simga receptors, which may induce subsequent activation of dopaminergic transmission.
我们研究了σ受体在可卡因诱导的行为敏化表达中的作用。大鼠连续14天每天接受一次腹腔注射20mg/kg可卡因或生理盐水。接受可卡因治疗的大鼠出现了敏化。在5天的戒断期后，给予一剂挑战剂量的σ受体激动剂（+）-3-[3-羟基苯基]-N-（1-丙基）哌啶（（+）-3-PPP）。与生理盐水预处理的大鼠相比，12mg/kg和24mg/kg剂量的（+）-3-PPP在可卡因敏化的大鼠中诱导出更频繁的竖毛行为以及由重复性头部运动和嗅探组成的更强的刻板行为。这些对（+）-3-PPP增强的反应持续了至少一个月。对（+）-3-PPP增强的反应被30mg/kg的推定σ拮抗剂BMY 14802减弱，也被100mg/kg的D2多巴胺拮抗剂（±）-舒必利减弱。这些发现表明，重复给予可卡因会产生持久的σ受体超敏反应，这可能会诱导随后多巴胺能传递的激活。
