Individual differences in cocaine seeking during voluntary abstinence predicts cocaine relapse and the circuitry mediating relapse.
Individual differences in cocaine seeking during voluntary abstinence predicts cocaine relapse and the circuitry mediating relapse.
复制标题
DOI：
10.1007/s00213-022-06270-x
复制
发表时间：
2022-12
影响因子：
3.4
通讯作者：
Knackstedt, Lori A.
中科院分区：
文献类型：
--
作者：
Padovan-Hernandez, Yasmin;Rojas, Giselle;Wu, Lizhen;Knackstedt, Lori A.
目前还没有FDA批准的治疗方法来促进可卡因使用障碍的恢复。应急管理提供非药物增强剂来鼓励戒毒，并在减少治疗期间寻求药物方面有效，但一旦停药，复发率就会增加。我们试图建立一种基于选择的可卡因自愿戒断(VA)的啮齿动物模型，以测试头孢曲松的能力，头孢曲松是一种一贯被证明可以防止啮齿动物对寻求可卡因的复发的抗生素，在VA停药后减轻复发的能力，并通过c-Fos的表达来研究复发诱导的神经元激活。雄性SD大鼠自我给予蔗糖粒5天，静脉注射可卡因12天。然后，大鼠接受了14天的自愿或强制禁欲。VA会议需要在不同的试验中在蔗糖和可卡因之间进行选择(每天20次试验)。在最后7天的禁欲期间给予头孢曲松(或赋形剂)。在复发测试中，只有与可卡因配对的操纵杆可用，按下操纵杆会发出与可卡因配对的提示。在VA期间，蔗糖杠杆受到的压力更多，但可卡因摄入量并没有下降到零。头孢曲松对VA期间的可卡因摄入量无影响。头孢曲松和维生素A都不会减少复发测试期间的可卡因寻求，而在接受车辆治疗的动物中，VA期间的可卡因摄入量与测试期间的可卡因寻求呈正相关。复发诱导的c-Fos在VA后的腹侧眶前皮质有更高的表达。蔗糖的供应导致可卡因寻求的减少，但不是停止，并导致潜在复发的回路的不同参与。
There are no FDA-approved treatments to facilitate recovery from cocaine use disorder. Contingency management offers non-drug reinforcers to encourage abstinence and is effective at reducing drug seeking during treatment, but once discontinued, relapse rates increase. We sought to establish a choice-based rodent model of voluntary abstinence (VA) from cocaine to test the ability of ceftriaxone, an antibiotic consistently shown to prevent relapse to cocaine seeking in rodents, to attenuate relapse after discontinuation of VA, and to investigate relapse-induced neuronal activation via c-Fos expression. Male Sprague–Dawley rats self-administered sucrose pellets for 5 days and intravenous cocaine for 12 days. Rats then underwent 14 days of voluntary or forced abstinence. VA sessions entailed the opportunity to choose between sucrose and cocaine delivery in discrete trials (20 trials/day). Ceftriaxone (or vehicle) was administered during the last 7 days of abstinence. During a relapse test, only the cocaine-paired lever was available and presses on the lever delivered cocaine-paired cues. There were more presses on the sucrose lever during VA, but cocaine intake did not decline to zero. Ceftriaxone had no effect on cocaine intake during VA. Neither ceftriaxone nor VA reduced cocaine seeking during the relapse test, and cocaine intake during VA positively correlated with cocaine seeking during the test in vehicle-treated animals. Relapse-induced c-Fos expression was found to be greater in the ventral orbitofrontal cortex following VA. Sucrose availability leads to a decrease in, but not cessation of, cocaine seeking and a differential engagement of the circuitry underlying relapse.
登录
查看更多内容
影响因子：
10.6
作者：
Caprioli D;Venniro M;Zeric T;Li X;Adhikary S;Madangopal R;Marchant NJ;Lucantonio F;Schoenbaum G;Bossert JM;Shaham Y
通讯作者：
Shaham Y
影响因子：
3.4
作者：
Alhaddad, Hasan;Das, Sujan C.;Sari, Youssef
通讯作者：
Sari, Youssef
DOI：
10.1523/jneurosci.1746-09.2009
发表时间：
2009-07-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Sari Y;Smith KD;Ali PK;Rebec GV
通讯作者：
Rebec GV
影响因子：
10.6
作者：
Knackstedt LA;Melendez RI;Kalivas PW
通讯作者：
Kalivas PW
影响因子：
3.4
作者：
Stevenson GW;Giuvelis D;Cormier J;Cone K;Atherton P;Krivitsky R;Warner E;St Laurent B;Dutra J;Bidlack JM;Szabò L;Polt R;Bilsky EJ
通讯作者：
Bilsky EJ