Matthews K, Baldo B A, Markou A, Lown O, Overstreet D H, Koob G F
Department of Experimental Psychology, University of Cambridge, UK.
Physiol Behav. 1996 Jun;59(6):1155-62. doi: 10.1016/0031-9384(95)02212-0.
Flinders Sensitive Line hypercholinergic rats, which exhibit augmented hypothermic responses to the cholinesterase inhibitor physostigmine and to the muscarinic agonist oxotremorine, have been proposed to represent a useful animal model for some aspects of human depression. With disturbance of reward processes considered to be a core feature of depression, the present studies were designed to investigate the neuropharmacology of brain stimulation-reward (BSR) in Flinders Sensitive Line (FSL) rats, Flinders Resistant Line (FRL) rats, and outbred control Sprague-Dawley rats. All animals were tested in a rate-free, current-threshold brain stimulation-reward paradigm, following acute challenges with the monoamine reuptake inhibitor cocaine, the dopamine D1 receptor antagonist SCH-23390, the cholinergic muscarinic antagonist scopolamine, and the serotonin reuptake inhibitor fluoxetine. Baseline BSR thresholds did not differ across the three groups. For all groups, cocaine lowered thresholds, SCH-23390 and scopolamine-elevated thresholds, while fluoxetine had no significant effect. Thresholds for the three groups were not differentially affected by pharmacological locomotor activity relative to outbred Sprague-Dawley controls. These results suggest that both Flinders lines exhibit behavioral differences from outbred control rats, but not with regard to reward processes as assessed by rewarding electrical stimulation of the lateral hypothalamus.
弗林德斯敏感品系的高胆碱能大鼠对胆碱酯酶抑制剂毒扁豆碱和毒蕈碱激动剂氧化震颤素表现出增强的低温反应，有人提出该品系可作为人类抑郁症某些方面的有用动物模型。鉴于奖赏过程的紊乱被认为是抑郁症的核心特征，本研究旨在调查弗林德斯敏感品系（FSL）大鼠、弗林德斯抗性品系（FRL）大鼠和远交对照斯普拉格-道利大鼠的脑刺激奖赏（BSR）的神经药理学。所有动物在无速率、电流阈值脑刺激奖赏范式中接受测试，在分别急性给予单胺再摄取抑制剂可卡因、多巴胺D1受体拮抗剂SCH-23390、胆碱能毒蕈碱拮抗剂东莨菪碱和5-羟色胺再摄取抑制剂氟西汀后进行测试。三组动物的基线BSR阈值没有差异。对所有组而言，可卡因降低了阈值，SCH-23390和东莨菪碱提高了阈值，而氟西汀没有显著影响。相对于远交斯普拉格-道利对照，三组动物的阈值并未因药物诱导的运动活动而受到不同影响。这些结果表明，两个弗林德斯品系与远交对照大鼠在行为上存在差异，但在下丘脑外侧奖赏性电刺激所评估的奖赏过程方面不存在差异。
