Del Arco Alberto, Zhu Shunwei, Terasmaa Anton, Mohammed Abdul H, Fuxe Kjell
Department of Neuroscience, Karolinska Institutet, 171 77, Stockholm, Sweden.
Psychopharmacology (Berl). 2004 Jan;171(2):148-55. doi: 10.1007/s00213-003-1578-8. Epub 2003 Sep 10.
Prolonged social isolation has been reported to induce different behavioral disturbances, among the most consistent of which are the increased locomotor response to novelty and the effects of psychostimulants. While these behavioral changes have been partly related to a dysregulation of dopaminergic activity in striatum (dorsal and ventral), the involvement of changes in the function of dopamine receptors is still a matter of controversy.
To investigate the effects of prolonged social isolation on the function of D2 receptors at both the behavioral and biochemical levels.
Sprague-Dawley rats were randomly placed at 21 days of age in groups or isolation for 2 months. Horizontal and vertical locomotor activities induced by novelty and also by systemic injections of the D2 agonist quinpirole (0.15, 0.50 and 1.5 mg/kg i.p.) and their modulation by the A2A agonist CGS 21680 (0.1 mg/kg i.p.) were studied. The effects of social isolation on the avoidance learning assessed by the passive avoidance test were also studied. Binding experiments were performed to study the number and affinity of D2 receptors by means of saturation and competition experiments with the D2 antagonist [(3)H]-raclopride and the interaction between D2 receptors and the G-protein by means of [(35)S]-GTPgammas binding in dorsal/ventral striatal membranes of both grouped and isolated rats.
Rats reared in isolation were hyperactive to a novel environment and showed shorter retention latencies in the passive avoidance test. Isolation rearing did not modify the increase in motor activity produced by quinpirole nor the counteraction of these effects by the simultaneous stimulation of A2A receptors. Likewise, the number, affinity and functional efficacy of D2 receptors were not changed by social isolation.
These results suggest that the hyperactivity to novelty and psychostimulants as well as other behavioral changes induced by social isolation do not parallel changes in the in vivo function or binding of D2 receptors in dorsal/ventral striatum.
据报道，长期的社会隔离会引发不同的行为障碍，其中最一致的表现是对新奇事物的运动反应增加以及精神兴奋剂的作用。虽然这些行为变化部分与纹状体（背侧和腹侧）多巴胺能活动失调有关，但多巴胺受体功能变化的参与仍存在争议。
在行为和生化水平上研究长期社会隔离对D2受体功能的影响。
将21日龄的Sprague-Dawley大鼠随机分组或隔离饲养2个月。研究新奇事物以及全身注射D2激动剂喹吡罗（0.15、0.50和1.5mg/kg腹腔注射）所诱导的水平和垂直运动活动，以及A2A激动剂CGS 21680（0.1mg/kg腹腔注射）对其的调节作用。还研究了社会隔离对通过被动回避试验评估的回避学习的影响。通过用D2拮抗剂[(3)H]-雷氯必利进行饱和和竞争实验来研究D2受体的数量和亲和力，并通过在分组和隔离大鼠的背侧/腹侧纹状体膜中进行[(35)S]-GTPγS结合来研究D2受体与G蛋白之间的相互作用。
隔离饲养的大鼠对新环境过度活跃，在被动回避试验中表现出较短的保留潜伏期。隔离饲养并未改变喹吡罗引起的运动活动增加，也未改变同时刺激A2A受体对这些作用的抵消作用。同样，社会隔离并未改变D2受体的数量、亲和力和功能效力。
这些结果表明，对新奇事物和精神兴奋剂的多动以及社会隔离引起的其他行为变化与背侧/腹侧纹状体中D2受体的体内功能或结合变化并不平行。
