A role for the prefrontal cortex in stress- and cocaine-induced reinstatement of cocaine seeking in rats
A role for the prefrontal cortex in stress- and cocaine-induced reinstatement of cocaine seeking in rats
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DOI：
10.1007/s00213-002-1283-z
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发表时间：
2003-07-01
影响因子：
3.4
通讯作者：
Stewart, J
中科院分区：
文献类型：
--
作者：
Capriles, N;Rodaros, D;Stewart, J
理由和目标在复发的动物模型中，压力诱导药物寻求的恢复是公认的。在这里，我们研究了内侧前额叶皮层（mPFC）和眶额皮层（OFC）在足电击应激诱导的可卡因寻求恢复中的作用。方法。训练各组大鼠自我施用可卡因（每次输注0.5mg/kg，静脉内，3小时/天，持续9天），并在10天无药后暴露于消退和恢复测试阶段。每60分钟的熄灭被30分钟的超时间隔，之后重新引入杠杆和刺激光。在第1天给予大鼠4次1小时消退，然后在随后的几天给予2至3次1小时消退，随后进行3小时恢复试验。每48小时进行一次测试。在一组实验中，通过河豚毒素（TTX，5 ng/0.5穆尔/侧）灭活前边缘（PL）、下边缘（IL）或OFC对由足部电击（5 min，间歇性，1 mA）或可卡因（20 mg/kg，i. p.）测定了在第二组中，使用相同的方法研究了D1样和D2样多巴胺受体拮抗剂（SCH 23390和雷氯必利）输注的影响。结果..将TTX注入PL皮质阻断了足休克和可卡因诱导的恢复。TTX进入OFC减弱足电击引起的，但不是可卡因引起的恢复。IL输注无效。PL或OFC输注SCH 22390（每侧0.25 μ g/0.5穆尔）可阻断足电击诱导的恢复，但PL输注对可卡因诱导的恢复无影响。雷氯必利（每侧5 μ g/0.5穆尔）对PL或OFC中足电击诱导的恢复没有影响，或者当注入PL时对可卡因诱导的恢复没有影响。TTX和SCH 23390注入PL或OFC对蔗糖的杠杆按压没有任何影响。结论.这些结果表明，PL和OFC区域形成的电路的一部分，介导的影响，足电击应力恢复药物寻求和PL区域可能是一个共同的途径线索，药物和足电击应力诱导恢复药物寻求。
Rationale and objective.. It is well established that stress induces reinstatement of drug seeking in an animal model of relapse. Here we studied the role of the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) in foot-shock stress-induced reinstatement of cocaine seeking. Methods.. Groups of rats were trained to self-administer cocaine (0.5 mg/kg per infusion, i.v., 3 h/day for 9 days) and after ten drug-free days were exposed to extinction and reinstatement test sessions. Each 60 min of extinction was separated by a 30-min time-out period after which the lever and stimulus lights were reintroduced. Rats were given four 1-h extinction sessions on day 1 and then on subsequent days were given two to three 1-h extinction sessions that were followed by a 3-h test for reinstatement. Tests were run every 48 h. In one set of experiments, the effects of inactivation of the prelimbic (PL), infralimbic (IL) or OFC by tetrodotoxin (TTX, 5 ng/0.5 mul per side) on reinstatement induced by foot shock (5 min, intermittent, 1 mA) or priming injections of cocaine (20 mg/kg, i.p.) were determined. In a second set, the effects of infusions of the D1-like and D2-like dopamine receptor antagonists (SCH 23390 and raclopride) were studied using the same methods. Results.. TTX infusions into the PL cortex blocked both foot shock and cocaine-induced reinstatement. TTX into OFC attenuated foot-shock-induced, but not cocaine-induced reinstatement. Infusions into IL were ineffective. Infusions of SCH 22390 (0.25 mug/0.5 mul per side) into either PL or OFC blocked foot-shock-induced reinstatement, but infusions into PL had no effect on cocaine-induced reinstatement. Raclopride (5 mug/0.5 mul per side) had no effect on foot-shock-induced reinstatement in either PL or OFC or on cocaine-induced reinstatement when infused into PL. Neither TTX nor SCH23390 infusions into PL or OFC had any effect on lever pressing for sucrose. Conclusions.. These results suggest that the PL and OFC regions form part of the circuitry mediating the effects of foot shock stress on reinstatement of drug seeking and that the PL region may be a common pathway for cue, drug and foot-shock stress-induced reinstatement of drug seeking.