Behavioral sensitization to Δ9-tetrahydrocannabinol and cross-sensitization with morphine:: differential changes in accumbal shell and core dopamine transmission
Behavioral sensitization to Δ9-tetrahydrocannabinol and cross-sensitization with morphine:: differential changes in accumbal shell and core dopamine transmission
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DOI：
10.1111/j.1471-4159.2008.05503.x
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发表时间：
2008-08-01
影响因子：
4.7
通讯作者：
Di Chiara, Gaetano
中科院分区：
文献类型：
--
作者：
Cadoni, Cristina;Valentini, Valentina;Di Chiara, Gaetano
虽然大麻素诱导的行为敏化和交叉致敏与阿片类药物最近已被证明，没有信息是可用的相关状态和多巴胺（DA）的传输在核壳（NAc）和核心的反应。在这项研究中，我们通过双探针微透析，研究暴露于Delta（9）-四氢大麻酚（Delta（9）-THC）和吗啡的致敏方案对基础条件下和在NAc壳和核中用Delta（9）-THC和吗啡激发后DA细胞外浓度的影响。给不同组的雄性Sprague-Dawley大鼠每天两次施用递增剂量的Δ（9）-THC（2、4和8 mg/kg腹膜内），持续3天，吗啡（10、20和40 mg/kg s.c.），和车辆。在最后一次注射14-20天后，动物被植入两个微透析探针，一个瞄准NAc壳，另一个瞄准核心。第二天，用150 μ g/kg的Delta（9）-THC静脉注射或0.5 mg/kg的吗啡静脉注射攻击用Delta（9）-THC和载体对照预处理的动物。用吗啡预处理的动物和它们的载体对照用150 μ g/kg的Delta（9）-THC静脉内给药。预先暴露于Delta（9）-THC的大鼠表现出与NAc壳中DA传递刺激减少和NAc核心中响应Delta（9）-THC攻击的刺激增加相关的行为敏化。预先暴露于Delta（9）-THC也诱导对吗啡的行为敏化，但仅观察到NAc壳中DA传递的刺激减少。用吗啡预处理的动物表现出行为敏化和响应于Delta（9）-THC攻击的NAc壳和核中DA的差异变化，其中壳中的反应降低，核中的反应增加。结果表明，Delta（9）-THC诱导的行为敏化与NAc亚区DA传递反应性的变化相关，这与其他滥用药物诱导的敏化中观察到的变化相似。
Although cannabinoid-induced behavioral sensitization and cross-sensitization with opiates has been recently demonstrated, no information is available on the associated state and responsiveness of dopamine (DA) transmission in the nucleus accumbens (NAc) shell and core. In this study we investigate by means of dual probe microdialysis, the effect of exposure to a sensitizing regimen of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and morphine on the extracellular concentrations of DA under basal conditions and after challenge with Delta(9)-THC and morphine in the NAc shell and core. Different groups of male Sprague-Dawley rats were administered twice daily for 3 days with increasing doses of Delta(9)-THC (2, 4, and 8 mg/kg i.p.), morphine (10, 20, and 40 mg/kg s.c.), and vehicle. After 14-20 days from the last injection, the animals were implanted with two microdialysis probes, one aimed at the NAc shell and the other at the core. The following day animals pre-treated with Delta(9)-THC and vehicle controls were challenged with 150 mu g/kg i.v. of Delta(9)-THC or 0.5 mg/kg i.v. of morphine. Animals pre-treated with morphine and their vehicle controls were administered with 150 mu g/kg i.v. of Delta(9)-THC. Rats pre-exposed to Delta(9)-THC showed behavioral sensitization associated with a reduced stimulation of DA transmission in the NAc shell and an increased stimulation in the NAc core in response to Delta(9)-THC challenge. Pre-exposure to Delta(9)-THC induced behavioral sensitization to morphine also, but only a reduced stimulation of DA transmission in the NAc shell was observed. Animals pre-treated with morphine showed behavioral sensitization and differential changes of DA in the NAc shell and core in response to Delta(9)-THC challenge with a decreased response in the shell and an increased response in the core. The results show that Delta(9)-THC-induced behavioral sensitization is associated with changes in the responsiveness of DA transmission in the NAc subdivisions that are similar to those observed in the sensitization induced by other drugs of abuse.