Kostrezewa R M, Klara J W, Robertson J, Walker L C
Department of Pharmacology, East Tennessee State University, Johnson City 37601.
Brain Res Bull. 1978 Sep-Oct;3(5):525-31. doi: 10.1016/0361-9230(78)90082-5.
The effect of various pharmacologic agents on the noradrenergic innervation of rat cerebellum was observed. It was found that the neurotoxin 6-hydroxydopa (6-OHDOPA), when given to rats at birth, caused a 46% reduction at 5 weeks of age in tyrosine hydroxylase activity in the locus coeruleus, the nucleus of origin for noradrenergic fibers innervating the cerebellum. At the same time, however, both tyrosine hydroxylase activity and NE content were elevated by 50% in the cerebellum. By treating gravid mice with the 6-OHDOPA, which crosses the placental barrier to affect the brains of developing pups, a dissociation has been shown between the elevated cerebellar NE levels and reduced telencephalic NE content. None of the other assorted pharmacological agents--namely amphetamine, metaraminol, apomorphine, alpha-methyl-p-tyrosine. L-dihydroxyphenylalanine and tyramine--when given at birth, caused a permanent elevation in cerebellar NE content. This series of studies suggests that a reduced number of noradrenergic perikarya are providing a greater innervation of the cerebellum than in control rats. Also, alteration of the telencephalic noradrenergic fibers, which are also derived from the locus coeruleus, does not appear to be a necessary event for the initiation of sprouting of noradrenergic fibers in the cerebellum. Because none of the acute-acting pharmacological agents caused a permanent elevation of NE in the cerebellum, it appears that damage, and not mere stimulation or blockade, is a necessary event for initiation of sprouting.
观察了各种药理制剂对大鼠小脑去甲肾上腺素能神经支配的影响。发现神经毒素6-羟基多巴胺（6-OHDOPA）在大鼠出生时给予，在5周龄时导致蓝斑中酪氨酸羟化酶活性降低46%，蓝斑是支配小脑的去甲肾上腺素能纤维的起源核。然而，与此同时，小脑中的酪氨酸羟化酶活性和去甲肾上腺素含量均升高了50%。通过用6-OHDOPA处理妊娠小鼠，6-OHDOPA可穿过胎盘屏障影响发育中小鼠的大脑，结果显示小脑去甲肾上腺素水平升高与端脑去甲肾上腺素含量降低之间存在分离。出生时给予的其他各种药理制剂，即苯丙胺、间羟胺、阿扑吗啡、α-甲基-对-酪氨酸、L-二羟基苯丙氨酸和酪胺，均未导致小脑去甲肾上腺素含量永久性升高。这一系列研究表明，与对照大鼠相比，去甲肾上腺素能神经元胞体数量减少，但对小脑的神经支配却增加。同样，也起源于蓝斑的端脑去甲肾上腺素能纤维的改变，似乎不是小脑去甲肾上腺素能纤维发芽起始的必要事件。由于没有一种急性作用的药理制剂能使小脑中的去甲肾上腺素永久性升高，因此看来损伤而非单纯的刺激或阻断，是发芽起始的必要事件。
