COORDINATE REGULATION OF THE CYCLIC-AMP SYSTEM WITH FIRING RATE AND EXPRESSION OF TYROSINE-HYDROXYLASE IN THE RAT LOCUS-CERULEUS - EFFECTS OF CHRONIC STRESS AND DRUG TREATMENTS
COORDINATE REGULATION OF THE CYCLIC-AMP SYSTEM WITH FIRING RATE AND EXPRESSION OF TYROSINE-HYDROXYLASE IN THE RAT LOCUS-CERULEUS - EFFECTS OF CHRONIC STRESS AND DRUG TREATMENTS
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DOI：
10.1111/j.1471-4159.1992.tb09748.x
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发表时间：
1992-02-01
影响因子：
4.7
通讯作者：
DUMAN, RS
中科院分区：
文献类型：
--
作者：
MELIA, KR;RASMUSSEN, K;DUMAN, RS
最近的研究表明，慢性应激可增加脑蓝斑核（LC）神经元中酪氨酸羟化酶（TH）的激活率和表达。蓝斑核是脑内主要的去肾上腺素能核。本研究旨在研究慢性应激和其他已知的治疗对LC神经元中cAMP第二信使系统活性的影响。正如之前报道的那样，慢性（5天）冷暴露显著增加了LC中TH免疫反应性的水平，但在黑质（SN）或腹侧被盖（VT）中没有，这是两种多巴胺能核的比较研究。慢性冷暴露增加了可溶性（而非颗粒）LC中camp依赖性蛋白激酶活性水平，并增加了该脑区基础和gtp和forskolin刺激的腺苷酸环化酶活性。相比之下，VT、SN和额叶皮层的蛋白激酶和腺苷酸环化酶水平不受冷暴露的显著影响。为了进一步研究LC放电速率、TH表达和LC中cAMP系统之间的关系，研究了已知影响TH的其他处理。利血平治疗，先前显示增加TH水平，被发现增加LC放电率和可溶性camp依赖性蛋白激酶活性水平。6-羟多巴胺，先前显示增加TH水平和LC神经元的放电率，也增加可溶性蛋白激酶活性水平。其他已知的增加（肾上腺切除术）或减少（慢性丙咪嗪）LC中TH水平的治疗也被发现分别增加或降低该脑区域camp依赖性蛋白激酶活性的水平。结果表明，慢性应激、儿茶酚胺耗竭以及各种药物和激素治疗对LC神经元放电速率、TH表达和cAMP系统的协调调节，并提出cAMP系统对这些治疗的适应有助于调节LC神经元放电和TH表达的可能性。
Recent studies have demonstrated that chronic stress increases the firing rate and expression of tyrosine hydroxylase (TH) in neurons of the locus coeruleus (LC), the major noradrenergic nucleus in brain. The present study was undertaken to examine the influence of chronic stress and other treatments known to influence the activity of LC neurons on the cyclic AMP (cAMP) second messenger system in these neurons. Chronic (5 days) cold exposure significantly increased levels of TH immunoreactivity in the LC, as previously reported, but not in substantia nigra (SN) or ventral tegmentum (VT), two dopaminergic nuclei studied for comparison. Chronic cold exposure increased levels of cAMP-dependent protein kinase activity in soluble, but not particulate, fractions of the LC, and increased basal and GTP-and forskolin-stimulated adenylate cyclase activity in this brain region. In contrast, levels of the protein kinase and adenylate cyclase in VT, SN, and frontal cortex were not significantly influenced by cold exposure. To study further the relationship between regulation of LC firing rate, TH expression, and the cAMP system in the LC, other treatments known to influence TH were examined. Reserpine treatment, shown previously to increase levels of TH, was found to increase both LC firing rate and levels of soluble cAMP-dependent protein kinase activity in the LC. 6-Hydroxydopamine, shown previously to increase levels of TH and firing rate of LC neurons, also increased soluble levels of protein kinase activity. Other treatments known to either increase (adrenalectomy) or decrease (chronic imipramine) levels of TH in the LC were also found to increase or decrease, respectively, levels of cAMP-dependent protein kinase activity in this brain region. The results demonstrate the coordinate regulation of LC firing rate, TH expression, and the cAMP system by chronic stress, catecholamine depletion, and various drug and hormone treatments and raise the possibility that adaptations in the cAMP system in response to these treatments contribute to regulation of LC neuronal firing and TH expression.