Denenberg Victor H, Kim Douglas S, Palmiter Richard D
Department of Biochemistry, University of Washington, Box 357370, Seattle, WA 98195-7370, USA.
Behav Brain Res. 2004 Jan 5;148(1-2):73-8. doi: 10.1016/s0166-4328(03)00183-9.
Dopamine-deficient (DD) mice have selective inactivation of the tyrosine hydroxylase gene in dopaminergic neurons, and they die of starvation and dehydration at 3-4 weeks of age. Daily injections of L-DOPA (50 mg/kg, i.p.) starting approximately 2 weeks after birth allow these animals to eat and drink enough for survival and growth. They are hyperactive for 6-9 h after receiving L-DOPA and become hypoactive thereafter. Because these animals can be tested in the presence or absence of DA, they were used to determine whether DA is necessary for learning to occur. DD mice were tested for learning to swim to an escape platform in a straight alley in the presence (30 min after an L-DOPA injection) or absence (22-24 h after an L-DOPA injection) of dopamine. The groups were split 24 h later and retested 30 min or 22-24 h after their last L-DOPA injection. In the initial test, DD mice without dopamine showed no evidence of learning, whereas those with dopamine had a learning curve similar in slope to controls but significantly slower. A retest after 24 h showed that DD mice can learn and remember in the absence of dopamine, leading to the inference that the lack of dopamine results in a performance/motivational decrement that masks their learning competence for this relatively simple task.
多巴胺缺乏（DD）小鼠的多巴胺能神经元中的酪氨酸羟化酶基因发生选择性失活，它们在3 - 4周龄时死于饥饿和脱水。从出生后约2周开始每天腹腔注射左旋多巴（L - DOPA，50 mg/kg）可使这些动物摄入足够的食物和水以维持生存和生长。它们在接受L - DOPA后6 - 9小时表现为多动，之后则活动减少。由于这些动物可以在有无多巴胺的情况下进行测试，因此被用于确定多巴胺对于学习的发生是否必要。DD小鼠在有（L - DOPA注射后30分钟）或无（L - DOPA注射后22 - 24小时）多巴胺的情况下，在直道中学习游向逃生平台进行测试。24小时后将这些组分开，并在最后一次L - DOPA注射后30分钟或22 - 24小时重新测试。在初始测试中，没有多巴胺的DD小鼠没有显示出学习的迹象，而有多巴胺的小鼠的学习曲线斜率与对照组相似，但明显较慢。24小时后的重新测试表明，DD小鼠在没有多巴胺的情况下也能学习和记忆，这导致推断多巴胺的缺乏导致了一种表现/动机的下降，掩盖了它们完成这项相对简单任务的学习能力。
