Kuroki T, Tsutsumi T, Hirano M, Matsumoto T, Tatebayashi Y, Nishiyama K, Uchimura H, Shiraishi A, Nakahara T, Nakamura K
Center for Emotional and Behavioral Disorders, Hizen National Mental Hospital, Saga, Japan.
Psychopharmacology (Berl). 1990;102(1):5-10. doi: 10.1007/BF02245736.
Repeated daily administration of an endogenous trace amine, beta-phenylethylamine (PEA), produces behavioral sensitization such that the intensity of PEA-induced stereotyped behaviors in rats increases gradually during the treatment, and a challenge injection with PEA reinstates the enhanced stereotypy even long after withdrawal. In the present study, we examined the neurochemical changes in the central dopaminergic neurons systems in the rat for 7 drug-free days after repeated treatment with PEA (50 mg/kg, IP day for 14 or 28 days). During withdrawal, a decrease in steady-state levels of tissue dopamine (DA) and its metabolite, dihydroxyphenylacetic acid (DOPAC), was found in the mesolimbic DA nerve terminal areas of the rat brain receiving repeated PEA treatment. Fifteen minutes after challenge administration of PEA at varying doses from 6.3 to 75 mg/kg, the rats with repeated PEA treatment required smaller doses of PEA challenge than the rats with acute PEA treatment in order to obtain a significant decrease in striatal DOPAC content compared to the saline control in each treatment group. These results imply that the behavioral sensitization to PEA is accompanied by enduring modifications of the specific dopaminergic neuron systems in the rat brain. This suggestion was strongly supported by the results of the study using in vivo intracerebral dialysis, which indicated that 25 mg/kg PEA challenge elicited a remarkable increase in the extracellular DA concentrations in striatal perfusates collected from the PEA-pretreated rats, in accordance with the intensity of stereotyped behaviors. These findings argue that the hyper-responsiveness to PEA of the striatal dopaminergic neuron systems persists long after withdrawal from repeated treatment with PEA.
每日重复给予内源性痕量胺β-苯乙胺（PEA）会产生行为敏化，即大鼠中PEA诱导的刻板行为强度在治疗期间逐渐增加，并且即使在撤药后很长时间，用PEA进行激发注射也会恢复增强的刻板行为。在本研究中，我们检查了用PEA（50mg/kg，腹腔注射，连续14或28天）重复治疗后大鼠中枢多巴胺能神经元系统在7天无药期的神经化学变化。在撤药期间，在接受重复PEA治疗的大鼠脑边缘中脑多巴胺（DA）神经终末区域发现组织DA及其代谢产物二羟基苯乙酸（DOPAC）的稳态水平降低。在用6.3至75mg/kg不同剂量的PEA进行激发给药后15分钟，与每种治疗组中的生理盐水对照相比，重复接受PEA治疗的大鼠为了使纹状体DOPAC含量显著降低所需的PEA激发剂量比急性接受PEA治疗的大鼠小。这些结果表明，对PEA的行为敏化伴随着大鼠脑中特定多巴胺能神经元系统的持久改变。使用体内脑内透析的研究结果有力地支持了这一观点，该结果表明，25mg/kg PEA激发引起从PEA预处理大鼠收集的纹状体灌流液中细胞外DA浓度显著增加，这与刻板行为的强度一致。这些发现表明，纹状体多巴胺能神经元系统对PEA的高反应性在从PEA重复治疗撤药后很长时间持续存在。
