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隔离饲养对下丘脑外侧区颅内自我刺激奖赏的影响:基线评估与药物激发试验

Effects of isolation-rearing on intracranial self-stimulation reward of the lateral hypothalamus: baseline assessment and drug challenges.

作者信息

Sundstrom J M, Hall F S, Stellar J R, Waugh E J

机构信息

Department of Psychology, Northeastern University, Boston, MA 02115, USA.

出版信息

Life Sci. 2002 Apr 26;70(23):2799-810. doi: 10.1016/s0024-3205(02)01509-6.

Abstract

There is evidence that isolation rearing produces down-regulation of the dopamine D2 receptor. Therefore, isolation rearing should also modify the effects of D2 antagonists on intracranial self-stimulation (ICSS) reward. This study investigated the effect of isolation rearing on ICSS reward, and modulation of that reward by SCH23390, Raclopride and MK-801. Sprague-Dawley rats were reared alone (isolates) or in pairs from day 21 postnatal to day 75 postnatal. At this time, all rats were implanted with monopolar stimulating electrodes in the lateral hypothalamus. The ICSS rate-frequency curve-shift method was used to assess reward and operant motor function at baseline and after administration of SCH-23390 (D1 antagonist: 0.02, 0.06, 0.2 mg/kg), Raclopride (D2 antagonist: 0.01, 0.025, 0.06 mg/kg), and MK-801 (non-competitive NMDA receptor antagonist: 0.1, 0.2 mk/kg). Isolation-reared rats displayed similar measures of both basal reward and motor function when compared to socially reared controls. Isolation-reared rats were subsensitive to the reward decreasing effects of Raclopride. Socially reared rats were observed to have more variant baseline reward measures, and could be divided into distinctly different groups with different basal reward function. Isolation-rearing down-regulates D2 function but does not affect basal reward function, but some unknown factor in the social rearing environment did have a substantial effect on basal reward function.

摘要

有证据表明,隔离饲养会导致多巴胺D2受体下调。因此,隔离饲养也应改变D2拮抗剂对颅内自我刺激(ICSS)奖赏的作用。本研究调查了隔离饲养对ICSS奖赏的影响,以及SCH23390、雷氯必利和MK - 801对该奖赏的调节作用。将Sprague-Dawley大鼠从出生后第21天至出生后第75天单独饲养(隔离组)或成对饲养。此时,所有大鼠均在下丘脑外侧植入单极刺激电极。采用ICSS率-频率曲线位移法评估基线时以及给予SCH - 23390(D1拮抗剂:0.02、0.06、0.2 mg/kg)、雷氯必利(D2拮抗剂:0.01、0.025、0.06 mg/kg)和MK - 801(非竞争性NMDA受体拮抗剂:0.1、0.2 mk/kg)后的奖赏和操作性运动功能。与群居饲养的对照相比,隔离饲养的大鼠在基础奖赏和运动功能方面表现出相似的指标。隔离饲养的大鼠对雷氯必利的奖赏降低作用不敏感。观察到群居饲养的大鼠基础奖赏指标变化更大,可分为具有不同基础奖赏功能的明显不同组。隔离饲养下调D2功能但不影响基础奖赏功能,但群居饲养环境中的一些未知因素确实对基础奖赏功能有显著影响。

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