SCH23390 and a humanized anti-cocaine mAb decrease the latency to cocaine-induced reinstatement of lever pressing behavior in rats that self-administer cocaine.
SCH23390 and a humanized anti-cocaine mAb decrease the latency to cocaine-induced reinstatement of lever pressing behavior in rats that self-administer cocaine.
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DOI：
10.1038/s41598-023-41284-1
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发表时间：
2023-09-04
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
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在自我注射可卡因的大鼠中，单剂量可卡因导致的杠杆按压行为恢复的潜伏期是由于可卡因水平下降到饱腹感阈值所需的时间。D1多巴胺受体拮抗剂SCH23390和重组人源化抗可卡因单抗h2E2提高了可卡因的饱腹感阈值，并有望改变恢复的潜伏期。雄性大鼠按照FR1时间表获得可卡因自我给药行为。这些大鼠接受一次可卡因注射(12微克/公斤体重静脉注射)。在静脉注射之后。注射SCH23390或输注h2E2或赋形剂。测量了杠杆按压的潜伏期和持续时间，但按压没有影响。SCH23390使小鼠按下杠杆的潜伏期缩短，与剂量依赖的饱腹感阈值增加一致。杠杆挤压行为的持续时间与SCH23390剂量成反比，表明SCH23390也增加了可卡因的强迫区。单抗h2E2也产生了类似的反应潜伏期的减少，并在2周内逐渐逆转。SCH23390和h2E2对可卡因诱导的杠杆按压潜伏期的缩短有相加作用。强迫区理论背景下的单一可卡因剂量恢复范式是探索预防可卡因使用障碍复发的潜在药物疗法的有用的药理生物测定系统。
In rats that self-administer cocaine, the latency to the reinstatement of lever pressing behavior induced by a single dose of cocaine is due to the time taken for cocaine levels to fall to the satiety threshold. The D1 dopamine receptor antagonist SCH23390, and the recombinant humanized anti-cocaine mAb h2E2 increase the cocaine satiety threshold and would be expected to alter the latency to reinstatement. Male rats acquired cocaine self-administration behavior on an FR1 schedule. These rats received a single injection of cocaine (12 µmol/kg i.v.) after an i.v. injection of SCH23390 or an infusion of h2E2 or vehicle. The latency to, and the duration of, lever pressing was measured but the presses had no consequence. SCH23390 decreased the latency to lever pressing consistent with dose-dependent increases in satiety threshold. The duration of lever pressing behavior was inversely proportional to the SCH23390 dose suggesting that SCH23390 also increased the cocaine compulsion zone. The mAb h2E2 also produced a similar decrease in latency to responding that gradually reversed over 2 weeks. SCH23390 and h2E2 had an additive effect on the decreased latency to cocaine-induced lever pressing. The single cocaine dose reinstatement paradigm within the context of the compulsion zone theory is a useful pharmacological bioassay system to explore potential pharmacotherapies for relapse prevention in cocaine use disorder.
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影响因子：
3
作者：
Norman, Andrew B.;Tabet, Michael R.;Norman, Mantana K.;Tsibulsky, Vladimir L.
通讯作者：
Tsibulsky, Vladimir L.
影响因子：
3.6
作者：
GERBER, GJ;STRETCH, R
通讯作者：
STRETCH, R
影响因子：
56.9
作者：
RITZ, MC;LAMB, RJ;KUHAR, MJ
通讯作者：
KUHAR, MJ
影响因子：
3.4
作者：
Khroyan, TV;Platt, DM;Spealman, RD
通讯作者：
Spealman, RD
影响因子：
4.2
作者：
Schenk, Susan;Hely, Lincoln;Daniela, Evangeline
通讯作者：
Daniela, Evangeline