Activational effects of social stress on IV cocaine self-administration in rats
Activational effects of social stress on IV cocaine self-administration in rats
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DOI：
10.1007/s002130050133
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发表时间：
1996-12-01
影响因子：
3.4
通讯作者：
Mutschler, NH
中科院分区：
文献类型：
--
作者：
Miczek, KA;Mutschler, NH
目前研究的目的是调查社会压力如何调节静脉注射可卡因的自我给药。具体地说，在大鼠身上制定了一项实验方案，评估了与攻击性对手反复发生的非损伤性社会对抗对随后可卡因自我给药行为的影响，并在一系列剂量范围内保持不变。最初，测定静脉注射可卡因的剂量-效应函数，每隔5个杠杆按压(固定比例或FR 5)加强一次，每个剂量(0.031、0.063、0.125、0.25 mg/次输注和生理盐水)至少评估3d。随后，这些大鼠被分配到两组，一组作为入侵者暴露在攻击性常驻大鼠的威胁下60分钟，同时受到筛子的保护，紧接着进行静脉自我给药，最多注射15次可卡因。第二组作为对照组，在没有任何社会压力暴露的情况下，被确定为第二个可卡因剂量效应功能。另外一些大鼠进行条件性杠杆挤压，食物强化的速度和模式与自身注射可卡因IV的特征非常相似(联合FI 3min FR 5)。反复发作的轻微社会压力增加了对可卡因强化杠杆的反应率。这种增加是在老鼠暴露在咄咄逼人的对手的威胁下后出现的，而不是在社交或单身住房之后。社会压力的这些行为激活效应(1)是长期的，(2)不受习惯化的影响，(3)对静脉注射可卡因强化的反应是选择性的，不延伸到非强化杠杆按压或食物强化杠杆按压，(4)在注射可卡因期间和之后的暂停期间最显著，(5)不缩短连续注射可卡因的间隔，以及(6)在低到中等剂量的可卡因时最为明显。这些结果表明，社会压力有效地激活了与寻找可卡因有关的运动常规，而不是增加了药物的增强效果。
The objective of the current studies was to investigate how social stress modulates IV cocaine self-administration. Specifically, an experimental protocol was developed in rats that assessed the impact of recurrent non-injurious social confrontations with an aggressive opponent on subsequent rate of cocaine self-administration behavior, maintained across a range of doses. Initially, the cocaine dose-effect function for intravenous self-administration was determined, reinforcing every fifth lever press (fixed ratio or FR 5), with each dose (0.031, 0.063, 0.125, 0.25 mg/infusion and saline) being assessed for at least 3 days. Subsequently, the rats were assigned to two groups, one group being exposed as intruders to the threats of an aggressive resident rat for 60 min, while being protected by a screen, immediately before a session for IV self-administration with maximally 15 cocaine infusions. A second group served as control, being determined for a second cocaine dose-effect function without any social stress exposure. Additional rats performed conditioned lever pressing that was reinforced by food at a rate and pattern closely similar to that characteristic for cocaine IV self-administration (joint FI 3 min FR 5). Recurrent episodes of mild social stress increased the rate of responding on the cocaine-reinforced lever. This increase is seen after rats have been exposed to the threats of an aggressive opponent, but not after social or single housing. These behaviorally activating effects of social stress (1) are long-lasting, (2) are not subject to habituation, (3) are selective to responding that is reinforced by IV cocaine, do not extend to non-reinforced lever pressing, or to food-reinforced lever pressing, (4) are most prominent in the time-out period during and after the cocaine infusion, (5) do not shorten the intervals between consecutive cocaine infusions, and (6) are most evident at lower to intermediate cocaine doses. These results suggest that social stress effectively activates the motor routines that are involved in cocaine-seeking rather than increasing the drug's reinforcing efficacy.