Breese G R, Baumeister A A, McCown T J, Emerick S G, Frye G D, Crotty K, Mueller R A
J Pharmacol Exp Ther. 1984 Nov;231(2):343-54.
Administration of L-dopa or apomorphine to neonatal and adult 6-hydroxydopamine (6-OHDA)-treated rats resulted in different behavioral responses depending on the age at which dopaminergic fibers were destroyed. When neonatal 6-OHDA-treated rats were tested as adults, they exhibited marked stereotypies, self-biting and self-mutilation behavior (SMB) when given these dopamine agonists. Self-biting as well as the incidence of SMB in neonatal 6-OHDA-treated rats showed dose-related changes between 10 and 100 mg/kg of L-dopa. This SMB and self-biting after L-dopa was observed as early as 22 to 24 days of age. Adult 6-OHDA-treated rats did not exhibit SMB or self-biting to L-dopa (100 mg/kg) or apomorphine (10 mg/kg), but did display paw treading and head nodding--behaviors not observed in neonatal 6-OHDA-treated rats. In addition, the locomotor response to apomorphine (1 mg/kg) was significantly greater in adult 6-OHDA-treated rats than in neonatal 6-OHDA-treated rats. Brain dopamine was reduced markedly in striatum, nucleus accumbens and olfactory tubercles in both 6-OHDA treatment groups with the reduction being slightly greater in rats treated with 6-OHDA neonatally. Serotonin content was elevated in striatum of rats treated neonatally with 6-OHDA, but not in adult 6-OHDA-treated rats. SMB and behaviors observed after L-dopa in rats treated neonatally with 6-OHDA were not apparent after L-dopa in rats with brain serotonin or norepinephrine reduced. Rats with brain dopaminergic fibers destroyed neonatally exhibited self-biting and SMB after L-dopa, suggesting that neonatal reduction of this amine is responsible for the SMB and self-biting in neonatal 6-OHDA-treated rats. 5-Hydroxytryptophan administration to neonatal 6-OHDA-treated rats did not induce SMB, indicating that release of serotonin by L-dopa is not responsible for this behavior. Because inhibition of dopamine-beta-hydroxylase did not alter the SMB response to L-dopa observed in neonatal 6-OHDA-treated rats, norepinephrine synthesized from L-dopa does not appear to contribute to the response. High doses of a decarboxylase inhibitor sufficient to inhibit conversion of dopa to dopamine in brain did not reduce the incidence of SMB. Administration of haloperidol (1 mg/kg) reduced the incidence of SMB, but did not antagonize the self-biting or the taffy pulling exhibited by L-dopa. In contrast, cisflupentixol completely blocked the SMB and self-biting induced by L-dopa.(ABSTRACT TRUNCATED AT 400 WORDS)
对新生和成年期经6-羟基多巴胺（6-OHDA）处理的大鼠给予左旋多巴或阿扑吗啡，会产生不同的行为反应，这取决于多巴胺能纤维被破坏时的年龄。当对新生期经6-OHDA处理的大鼠成年后进行测试时，给予这些多巴胺激动剂后，它们会表现出明显的刻板行为、自咬和自残行为（SMB）。新生期经6-OHDA处理的大鼠的自咬以及SMB发生率在左旋多巴剂量为10至100mg/kg之间呈现出剂量相关的变化。早在22至24日龄时就能观察到左旋多巴给药后的这种SMB和自咬行为。成年期经6-OHDA处理的大鼠对左旋多巴（100mg/kg）或阿扑吗啡（10mg/kg）未表现出SMB或自咬行为，但确实表现出爪踏和点头行为，而这些行为在新生期经6-OHDA处理的大鼠中未观察到。此外，成年期经6-OHDA处理的大鼠对阿扑吗啡（1mg/kg）的运动反应明显大于新生期经6-OHDA处理的大鼠。在两个6-OHDA处理组中，纹状体、伏隔核和嗅结节中的脑多巴胺均显著降低，新生期接受6-OHDA处理的大鼠中降低幅度略大。新生期经6-OHDA处理的大鼠纹状体中的血清素含量升高，但成年期经6-OHDA处理的大鼠中未升高。脑血清素或去甲肾上腺素降低的大鼠在给予左旋多巴后未出现新生期经6-OHDA处理的大鼠在给予左旋多巴后所观察到的SMB和行为。新生期脑多巴胺能纤维被破坏的大鼠在给予左旋多巴后表现出自咬和SMB行为，这表明新生期该胺类物质的减少是新生期经6-OHDA处理的大鼠出现SMB和自咬行为的原因。对新生期经6-OHDA处理的大鼠给予5-羟色氨酸不会诱导SMB，这表明左旋多巴释放血清素并非该行为的原因。因为抑制多巴胺-β-羟化酶并未改变新生期经6-OHDA处理的大鼠对左旋多巴的SMB反应，所以由左旋多巴合成的去甲肾上腺素似乎对该反应没有贡献。高剂量足以抑制脑中多巴转化为多巴胺的脱羧酶抑制剂并未降低SMB的发生率。给予氟哌啶醇（1mg/kg）可降低SMB的发生率，但并未拮抗左旋多巴引起的自咬或拉糖行为。相比之下，顺式氟奋乃静完全阻断了左旋多巴诱导的SMB和自咬行为。（摘要截选至400字）
