Changes in response to a dopamine receptor antagonist in rats with escalating cocaine intake
Changes in response to a dopamine receptor antagonist in rats with escalating cocaine intake
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DOI：
10.1007/s00213-003-1682-9
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发表时间：
2004-04-01
影响因子：
3.4
通讯作者：
Koob, GF
中科院分区：
文献类型：
--
作者：
Ahmed, SH;Koob, GF
理由和目标。延长可卡因自我给药（长接触或 LgA）会导致药物摄入量增加，而在有限接触药物（短接触或 ShA）的情况下则不会观察到这种情况。本研究检验了可卡因使用的增加与多巴胺神经传递的慢性改变有关的假设。方法。在增加可卡因自我给药后，ShA和LgA大鼠接受不同皮下剂量的顺式氟哌噻吨（10-270μg/kg）（一种高选择性多巴胺受体拮抗剂）的攻击。结果。在两组中，增加顺式氟哌噻吨剂量首先导致可卡因注射次数增加，然后导致行为显着抑制。这种双相剂量效应函数（复制了该实验室之前的发现）相对于 ShA 大鼠在 LgA 大鼠中向左移动，从而降低了行为被完全抑制的阈剂量。结论。这些数据支持这样的假设：多巴胺神经传递的改变导致可卡因自我给药的增加。
Rationale and objectives. Prolonged access to cocaine self-administration (long access or LgA) produces an escalation in drug intake not observed with limited access to the drug (short access or ShA). The present study tested the hypothesis that escalating use of cocaine is associated with chronic alterations in dopamine neurotransmission. Methods. After escalation of cocaine self-administration, ShA and LgA rats were challenged with different subcutaneous doses of cis-flupenthixol (10-270 mug/kg), a highly selective dopamine receptor antagonist. Results. In both groups, increasing doses of cis-flupenthixol first produced an increase in the number of cocaine injections and then a dramatic suppression of behavior. This biphasic dose-effect function-which replicates previous findings from this laboratory-was shifted to the left in LgA rats relative to ShA rats, thereby decreasing the threshold dose at which behavior was completely suppressed. Conclusions. These data support the hypothesis that alterations in dopamine neurotransmission contribute to escalation of cocaine self-administration.