Blockade of D2 dopamine receptors in the VTA induces a long-lasting enhancement of the locomotor activating effects of amphetamine.
Blockade of D2 dopamine receptors in the VTA induces a long-lasting enhancement of the locomotor activating effects of amphetamine.
复制标题
阻断 VTA 中的 D2 多巴胺受体可诱导苯丙胺的运动激活作用持久增强。
DOI：
10.1097/00008877-200409000-00013
复制
发表时间：
2004
影响因子：
1.6
通讯作者：
Vezina,P
中科院分区：
文献类型：
--
作者：
Tanabe,LM;Suto,N;Creekmore,E;Steinmiller,CL;Vezina,P
The present study examined the effects of pre-exposure to eticlopride, a D 2 dopamine receptor antagonist, in the ventral tegmental area (VTA) on the subsequent locomotor activating effects of amphetamine (AMPH). Rats were pre-exposed to one of three doses of eticlopride (0.75, 3.0 or 12.0 μg/0.5 μl per side) or saline (0.5 μl/side) in the VTA, once every third day, for a total of three infusions. Locomotor activity was recorded for 2 h following each pre-exposure injection. The low and intermediate doses of eticlopride produced no effects, while the high dose decreased locomotor activity compared to saline controls. 10–14 days following the last pre-exposure injection, all rats were challenged with AMPH (1.0 mg/kg, ip) and locomotor activity was recorded. Rats pre-exposed to the low dose of eticlopride exhibited enhanced locomotor activity whereas those pre-exposed to the intermediate or high doses did not differ from saline pre-exposed controls, suggesting that blockade of D 2 dopamine receptors in the VTA can lead to sensitized locomotor responding to AMPH. To investigate the possible mechanism by which the low dose of eticlopride induced sensitization, extracellular levels of dopamine were measured as increasing concentrations of eticlopride (0.1, 1.0, 10.0 and 100.0 μmol/l) were perfused through a microdialysis probe implanted in the VTA. Only the lowest eticlopride concentration elevated extracellular dopamine levels. Therefore, as in the case of AMPH-induced sensitization, the induction by eticlopride of sensitization to AMPH may be initiated by the ability of eticlopride to increase extracellular levels of dopamine in the VTA.
