The neuropeptides oxytocin (OT) and vasopressin (AVP) are recognized for their modulation of social processes in humans when delivered peripherally. However, there is surprisingly little evidence for acute social effects of peripherally administered OT or AVP in animal models. On the other hand, the party drug 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') has powerful prosocial effects in rats that appear to occur through stimulation of central OT release. Here, we directly compared the social effects of peripherally administered OT and AVP with those of MDMA, and examined a possible role for the vasopressin 1A receptor (V1AR) in the observed prosocial effects. Adult male Long-Evans rats were tested in a social interaction paradigm after OT (0.1, 0.25, 0.5, and 1 mg/kg, intraperitoneal (IP)), AVP (0.001, 0.0025, 0.005, 0.01, and 0.1 mg/kg, IP), and MDMA (2.5, 5 mg/kg, IP), or combined low doses of OT and MDMA, or AVP and MDMA. The effects of pretreatment with the non-peptide OT receptor antagonist compound 25 (C25; 5 mg/kg, IP) and the V1AR antagonist SR49059 (1 mg/kg, IP) were also examined. OT (0.5 mg/kg), AVP (0.01 mg/kg), and MDMA (5 mg/kg) potently increased 'adjacent lying', where rats meeting for the first time lie passively next to each other. C25 did not inhibit adjacent lying induced by OT, whereas SR49059 inhibited adjacent lying induced by MDMA (5 mg/kg), OT (0.5 mg/kg), and AVP (0.01 mg/kg). Interestingly, when ineffective doses of OT and MDMA, or AVP and MDMA, were combined, a robust increase in adjacent lying was observed. These results show for the first time acute prosocial effects of peripherally injected OT and AVP in laboratory rats, and suggest a commonality of action of OT, AVP, and MDMA in stimulating social behavior that involves V1ARs.

译文

神经肽催产素 (OT) 和加压素 (AVP) 因其在外周递送时对人类社会过程的调节而被认可。然而,在动物模型中,几乎没有证据表明外周施用OT或AVP的急性社会影响。另一方面,方药3,4-亚甲二氧基甲基苯丙胺 (MDMA,'Ecstasy') 在大鼠中具有强大的亲社会作用,似乎是通过刺激中央OT释放而发生的。在这里,我们直接比较了外周给予OT和AVP与MDMA的社会效应,并研究了加压素1A受体 (V1AR) 在观察到的亲社会效应中的可能作用。成年雄性Long-Evans大鼠在OT (0.1、0.25、0.5和1 mg mg/kg,腹膜内 (IP)),AVP (0.001、0.0025、0.005、0.01和0.1  mg/kg,IP) 和MDMA (2.5,5  mg/kg,IP),或联合低剂量OT和MDMA,或AVP和MDMA。还研究了非肽OT受体拮抗剂化合物25 (C25; 5  mg/kg,IP) 和V1AR拮抗剂SR49059 (1  mg/kg,IP) 的预处理效果。OT (0.5  mg/kg) 、AVP (0.01  mg/kg) 和MDMA (5  mg/kg) 有效地增加了 “相邻的裂隙”,即第一次相遇的大鼠被动地彼此相邻。C25不抑制OT诱导的相邻卧位,而SR49059抑制MDMA (5  mg/kg) 、OT (0.5  mg/kg) 和AVP (0.01  mg/kg) 诱导的相邻卧位。有趣的是,当将无效剂量的OT和MDMA或AVP和MDMA组合在一起时,观察到相邻卧位的显着增加。这些结果首次显示了在实验室大鼠中外周注射OT和AVP的急性亲社会作用,并表明OT,AVP和MDMA在刺激涉及v1ar的社会行为方面的作用具有共性。

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