Ahmed Serge H, Koob George F
Laboratoire de Neuropsychobiologie Desadaptations, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5541, Universite Victor Segalen Bordeaux 2, Bordeaux, France.
Psychopharmacology (Berl). 2004 Apr;172(4):450-4. doi: 10.1007/s00213-003-1682-9. Epub 2003 Nov 28.
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.
After escalation of cocaine self-administration, ShA and LgA rats were challenged with different subcutaneous doses of cis-flupenthixol (10-270 micro g/kg), a highly selective dopamine receptor antagonist.
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.
These data support the hypothesis that alterations in dopamine neurotransmission contribute to escalation of cocaine self-administration.
长期可获得可卡因自我给药（长时程给药或LgA）会导致药物摄入量增加，而限制药物获取（短时程给药或ShA）则不会出现这种情况。本研究检验了可卡因使用量增加与多巴胺神经传递慢性改变有关这一假设。
在可卡因自我给药量增加后，对ShA组和LgA组大鼠皮下注射不同剂量（10 - 270微克/千克）的顺式氟哌噻吨，这是一种高选择性多巴胺受体拮抗剂。
在两组中，顺式氟哌噻吨剂量增加首先会使可卡因注射次数增加，随后行为受到显著抑制。这种双相剂量效应函数——重复了本实验室之前的研究结果——在LgA组大鼠中相对于ShA组大鼠向左偏移，从而降低了行为被完全抑制时的阈值剂量。
这些数据支持了多巴胺神经传递改变导致可卡因自我给药量增加这一假设。
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