Miczek K A, Mutschler N H
Tufts University, Medford, MA 02155, USA.
Psychopharmacology (Berl). 1996 Dec;128(3):256-64. doi: 10.1007/s002130050133.
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.
当前研究的目的是探究社会压力如何调节静脉注射可卡因的自我给药行为。具体而言，在大鼠中制定了一个实验方案，评估与具有攻击性的对手反复进行无伤害性社会对抗对后续可卡因自我给药行为速率的影响，该行为在一系列剂量下得以维持。首先，确定静脉自我给药的可卡因剂量效应函数，每按压杠杆五次（固定比率或FR 5）给予强化，对每个剂量（0.031、0.063、0.125、0.25毫克/输注以及生理盐水）至少评估3天。随后，将大鼠分为两组，一组作为入侵者在静脉自我给药环节（最多15次可卡因输注）前立即暴露于具有攻击性的常住大鼠的威胁下60分钟，同时受到隔板保护。第二组作为对照组，在没有任何社会压力暴露的情况下确定第二个可卡因剂量效应函数。另外的大鼠进行条件性杠杆按压，以与可卡因静脉自我给药特征密切相似的速率和模式给予食物强化（联合FI 3分钟FR 5）。反复的轻度社会压力发作增加了对可卡因强化杠杆的反应速率。这种增加在大鼠暴露于具有攻击性的对手的威胁后出现，但在群居或单笼饲养后未出现。社会压力的这些行为激活作用（1）是持久的，（2）不会产生习惯化，（3）对静脉注射可卡因强化的反应具有选择性，不会扩展到未强化的杠杆按压或食物强化的杠杆按压，（4）在可卡因输注期间和之后的暂停期最为突出，（5）不会缩短连续可卡因输注之间的间隔，并且（6）在较低至中等可卡因剂量下最为明显。这些结果表明，社会压力有效地激活了与寻求可卡因相关的运动程序，而不是增加药物的强化效力。
