Alpha-noradrenergic receptors modulate the development and expression of cocaine sensitization
Alpha-noradrenergic receptors modulate the development and expression of cocaine sensitization
复制标题
DOI：
10.1196/annals.1369.039
复制
发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Vazquez-Torres, Rafael
中科院分区：
文献类型：
--
作者：
Jimenez-Rivera, Carlos A.;Feliu-Mojer, Monica;Vazquez-Torres, Rafael
由于重复服用可卡因而导致的活动增加和刻板行为被称为可卡因致敏。这种致敏反应被认为是药物成瘾的基本病理生理机制之一。最近的证据表明去甲肾上腺素能神经传递可能与可卡因的某些行为效应有关。本文研究了α-肾上腺素能受体激动剂和拮抗剂在可卡因致敏的发展和表达中的作用。给大鼠腹腔注射α-1受体拮抗剂哌唑嗪（0.5mg/kg），每天1次，连续7天。可卡因给药前15分钟（15 mg/kg，i. p.）。8天后，动物接受可卡因攻击（15 mg/kg，i. p.）并进行了运动测试在7天的戒断期后，大鼠接受第二次可卡因激发。最后一次激发后1天，将大鼠恢复至初始方案1天。在另一组实验中，每天两次给大鼠注射α-2受体拮抗剂育亨宾（5 mg/kg，i. p.），咪唑克生（0.25mg/kg，i. p.），或与α-2激动剂可乐定（0.025 mg/kg，i. p.），随后注射可卡因（15 mg/kg，腹膜内），连续7天。此后，方案与哌唑嗪给药后相似。结果表明，α-1受体拮抗剂哌唑嗪阻断可卡因致敏的发展和表达。另一方面，两种α-2拮抗剂均未能抑制可卡因致敏的发展或表达。相反，他们在实验的第一天增加了自发活动。α-2激动剂可乐定减弱可卡因的急性反应，在第1天，并推迟增加的自发活动在接下来的2天。在第一次可卡因激发后，致敏水平急剧增加。然而，它抑制可卡因致敏的表达在恢复协议。这些结果表明，α肾上腺素受体在调节可卡因致敏和可卡因成瘾的不同阶段中起着重要作用。
The increased activity and stereotyped behaviors that result from repeated administration of cocaine is called cocaine sensitization. This sensitized response has been postulated as one of the basic pathophysiological mechanisms in drug addiction. Recent evidence indicates that noradrenergic neurotransmission might be implicated in some of the behavioral effects of cocaine. The present article examined the role of alpha-adrenergic receptor agonists and antagonists in the development and expression of cocaine sensitization. Rats were injected once per day, for 7 consecutive days, with the alpha-1 receptor antagonist prazosin (0.5 mg/kg, i.p.) 15 min before cocaine administration (15 mg/kg, i.p.). After 8 days, animals received a cocaine challenge (15 mg/kg, i.p.) and were tested for locomotion. Following a 7-day withdrawal period rats received a second cocaine challenge. One day after the last challenge, rats were reinstated to the initial protocol for 1 day. In another set of experiments, rats were injected twice per day with the alpha-2 receptor antagonists yohimbine (5 mg/kg, i.p.), idazoxan (0.25 mg/kg, i.p.), or with the alpha-2 agonist clonidine (0.025 mg/kg, i.p.), followed by cocaine injections (15 mg/kg, i.p.), for 7 consecutive days. Thereafter, the protocol was similar to that following prazosin administration. The results demonstrated that the alpha-1 receptor antagonist prazosin blocked the development and expression of cocaine sensitization. On the other hand, both alpha-2 antagonists failed to inhibit the development or the expression of cocaine sensitization. Instead, they produced an increase in locomotor activity during the first day of experimentation. The alpha-2 agonist clonidine attenuated the acute response to cocaine on day 1 and retarded the increased locomotor activity on the following 2 days. There was a dramatic increase in the level of sensitization after the first cocaine challenge. However, it inhibited the expression of cocaine sensitization during the reinstatement protocol. These results suggest that alpha adrenoreceptors play an important role in modulating different stages of cocaine sensitization and probably cocaine addiction.