Department of Psychiatry, Psychotherapy and Psychosomatics, Division of Psychiatry I, Medical University Innsbruck, Innsbruck, Austria.
Institute of Molecular Biology, University of Innsbruck, Innsbruck, Austria.
Addict Biol. 2021 Jan;26(1):e12878. doi: 10.1111/adb.12878. Epub 2020 Jan 26.
Social interaction in an alternative context can be beneficial against drugs of abuse. Stress is known to be a risk factor that can exacerbate the effects of addictive drugs. In this study, we investigated whether the positive effects of social interaction are mediated through a decrease in stress levels. For that purpose, rats were trained to express cocaine or social interaction conditioned place preference (CPP). Behavioural, hormonal, and molecular stress markers were evaluated. We found that social CPP decreased the percentage of incorrect transitions of grooming and corticosterone to the level of naïve untreated rats. In addition, corticotropin-releasing factor (CRF) was increased in the bed nucleus of stria terminalis after cocaine CPP. In order to study the modulation of social CPP by the CRF system, rats received intracerebroventricular CRF or alpha-helical CRF, a nonselective antagonist of CRF receptors. The subsequent effects on CPP to cocaine or social interaction were observed. CRF injections increased cocaine CPP, whereas alpha-helical CRF injections decreased cocaine CPP. However, alpha-helical CRF injections potentiated social CPP. When social interaction was made available in an alternative context, CRF-induced increase of cocaine preference was reversed completely to the level of rats receiving cocaine paired with alpha-helical CRF. This reversal of cocaine preference was also paralleled by a reversal in CRF-induced increase of p38 MAPK expression in the nucleus accumbens shell. These findings suggest that social interaction could contribute as a valuable component in treatment of substance use disorders by reducing stress levels.
社交互动在替代环境中可能对滥用药物有益。压力是已知的风险因素,可以加剧成瘾药物的作用。在这项研究中,我们研究了社交互动的积极作用是否通过降低压力水平来介导。为此,训练大鼠表达可卡因或社交互动条件位置偏好(CPP)。评估了行为、激素和分子应激标志物。我们发现社交 CPP 降低了梳理和皮质酮向未处理的天真大鼠水平的错误过渡的百分比。此外,可卡因 CPP 后终纹床核中的促肾上腺皮质释放因子(CRF)增加。为了研究 CRF 系统对社交 CPP 的调制,大鼠接受了脑室内 CRF 或 α-螺旋 CRF,CRF 受体的非选择性拮抗剂。随后观察了对可卡因或社交互动的 CPP 的影响。CRF 注射增加了可卡因 CPP,而 α-螺旋 CRF 注射降低了可卡因 CPP。然而,α-螺旋 CRF 注射增强了社交 CPP。当社交互动在替代环境中可用时,CRF 诱导的可卡因偏好增加完全逆转至接受与 α-螺旋 CRF 配对的可卡因的大鼠水平。可卡因偏好的这种逆转也与核壳 Accumbens 中 CRF 诱导的 p38 MAPK 表达增加的逆转平行。这些发现表明,社交互动通过降低压力水平,可能作为治疗物质使用障碍的有价值的组成部分。