The dopamine D2/D3 antagonist DS121 potentiates the effect of cocaine on locomotion and reduces tolerance in cocaine tolerant rats.
The dopamine D2/D3 antagonist DS121 potentiates the effect of cocaine on locomotion and reduces tolerance in cocaine tolerant rats.
复制标题
多巴胺 D2/D3 拮抗剂 DS121 增强可卡因对运动的影响，并降低可卡因耐受大鼠的耐受性。
DOI：
10.1016/s0166-4328(00)00270-9
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发表时间：
2000
影响因子：
2.7
通讯作者：
Lee,TH
中科院分区：
文献类型：
--
作者：
Ellinwood,EH;King,GR;Davidson,C;Lee,TH
To explore the significance of dopamine (DA) autoreceptors in cocaine tolerance and cocaine induced locomotor activity rats were treated with saline and cocaine (40 mg/kg per day via osmotic minipump; normal and cocaine tolerant rats, respectively). Injections of DS121 (0–7 mg/kg, i.p.; S(-)-3-(3-(cyanophenyl)-N-n-propylpiperidine), a DA D2/3and autoreceptor preferring antagonist, either alone (i.e. DS121+saline injection) or in combination with cocaine (7.5 mg/kg, i.p.) were also given. DS121 (+saline) increased locomotor activity in both saline and cocaine pump (CP) treated animals. DS121 also potentiated the effect of cocaine on locomotor activity; this effect was greatest in CP (tolerant) animals. It is concluded that DS121 can increase locomotor activity and that this effect is greatest when the DA tone is high, that is when cocaine is present, suggestive of a presynaptic mechanism. Furthermore, because DS121 potentiation of cocaine induced locomotor activity is greatest in tolerant animals it is concluded that supersensitive DA autoreceptors underlie this effect. These data further support our previous data, which show that DA autoreceptors are sensitized after continuous cocaine (minipump) treatment.
