化学
阿扑吗啡
浣熊
药理学
兴奋剂
伏隔核
甲基苯丙胺
敏化
受体
多巴胺受体D2
受体拮抗剂
多巴胺受体
多巴胺能
内科学
内分泌学
多巴胺
敌手
神经科学
生物
医学
生物化学
作者
Ji-Hoon Yoo,Ha-Kyung Lee,Hyoung-Chun Kim,Seok-Yong Lee,Choon-Gon Jang
出处
期刊:Synapse
[Wiley]
日期:2010-04-01
卷期号:64 (4): 274-279
被引量:10
摘要
We previously showed that 5-HT(3) receptors are involved in the development and expression of methamphetamine (MAP)-induced locomotor sensitization in mice. Here, we examined whether the dopaminergic or the GABAergic systems are involved in the attenuating effects of the 5-HT(3) receptor antagonist MDL72222 on MAP-induced locomotor sensitization. Quantitative autoradiography of D1 ([(3)H]SCH23390), D2 ([(3)H]raclopride) receptor, and GABA(A) receptor benzodiazepine ([(3)H]flunitrazepam) binding was carried out in the brains of mice treated with chronic MAP and pretreatment with MDL72222. No significant differences were found in D(1) and D(2) binding between the two groups, suggesting that the attenuating effects of MDL72222 on MAP-induced locomotor sensitization is not medicated by D1 and D2 receptors. Postsynaptic dopamine (DA) receptor supersensitivity was measured by challenge with apomorphine, a dopamine D(1) and D(2) receptor agonist, after repeated MAP treatment or pretreatment with MDL72222 before MAP. Apomorphine induced an enhanced locomotor activity in both chronic MAP-treated mice and mice pretreated with MDL 72222, with no significant differences between the two groups. The binding of [(3)H]flunitrazepam was significantly decreased in the motor and cingulate cortex, caudate putamen, and nucleus accumbens of mice in the repeated MAP treatment group compared with the control group, and this effect was reversed by pretreatment with MDL72222. This suggested that GABA(A) benzodiazepine binding sites are involved in the attenuating effects of a 5-HT(3) receptor antagonist on MAP-induced locomotor sensitization.
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