Spangler E L, Wenk G L, Chachich M E, Smith K, Ingram D K
Laboratory of Cellular and Molecular Biology, Nathan W. Shock Laboratories, National Institute on Aging, Francis Scott Key Medical Center, Baltimore, Maryland 21224.
Behav Neurosci. 1990 Jun;104(3):410-7. doi: 10.1037//0735-7044.104.3.410.
Noradrenergic (NA) involvement in acquisition (AQ) and retention (RET) of a shock-motivated 14-unit T-maze after intraperitoneal (ip) administration of DSP4, a neurotoxin that depletes forebrain NA, was evaluated in 2 experiments using 3-month-old male F-344 rats. Depletion of cortical NA level in DSP4-treated rats was verified by neurochemical assay and by latency to postdecapitation clonus reflex. In Experiment 1, DSP4 (50 mg/kg ip) rats did not differ from saline-treated (SAL) rats on any measure of maze performance (errors, alternation errors, run time, shock duration, or shock frequency) during AQ (DSP4 2 weeks prior to testing) nor during a RET test 2-3 weeks later (DSP4 immediately after the last AQ trial or 1 week after AQ). In Experiment 2, DSP4 and scopolamine (SCOP), a cholinergic (ACh) antagonist, were administered in combination to test for an NA-ACh interaction. DSP4 (50 mg/kg ip 2 weeks prior to AQ) again had no effect on AQ performance nor did DSP4 interact with either dose of SCOP (0.25 or 0.5 mg/kg ip 30 min prior to AQ) to further impair performance. Similar to previous studies SCOP impaired all measures of maze performance except shock duration. These experiments provide further evidence for involvement of ACh systems in the learning of this task and in the age-related impairments previously observed, but they suggest that central NA systems may not be involved directly or interactively with ACh systems required for efficient performance in this maze.
使用3个月大的雄性F-344大鼠,在2个实验中评估了去甲肾上腺素能(NA)在腹腔注射(ip)DSP4(一种可耗尽前脑NA的神经毒素)后对电击驱动的14单元T迷宫习得(AQ)和记忆保持(RET)的影响。通过神经化学测定和断头后阵挛反射潜伏期,验证了DSP4处理大鼠的皮质NA水平的耗尽情况。在实验1中,DSP4(50mg/kg腹腔注射)大鼠在AQ期间(测试前2周给予DSP4)以及2 - 3周后的RET测试期间(最后一次AQ试验后立即给予DSP4或AQ后1周),在迷宫表现的任何指标(错误次数、交替错误次数、奔跑时间、电击持续时间或电击频率)上与生理盐水处理(SAL)大鼠均无差异。在实验2中,联合给予DSP4和东莨菪碱(SCOP,一种胆碱能(ACh)拮抗剂)以测试NA - ACh相互作用。DSP4(AQ前2周50mg/kg腹腔注射)同样对AQ表现没有影响,且DSP4与任何剂量的SCOP(AQ前30分钟0.25或0.5mg/kg腹腔注射)均未相互作用以进一步损害表现。与先前研究相似,SCOP损害了迷宫表现的所有指标,但电击持续时间除外。这些实验为ACh系统参与该任务的学习以及先前观察到的与年龄相关的损害提供了进一步证据,但表明中枢NA系统可能不直接参与或与该迷宫中高效表现所需的ACh系统相互作用。