Melega W P, Raleigh M J, Stout D B, Huang S C, Phelps M E
Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095-1735, USA.
Behav Brain Res. 1997 Mar;84(1-2):259-68. doi: 10.1016/s0166-4328(97)83333-5.
A chronic 10-day amphetamine (Amp) protocol was used to induce significant long-term decrements of the striatal [18F]fluoro-L-DOPA influx rate constant (FDOPA Ki) in the vervet monkey. Longitudinal FDOPA-positron emission tomography (PET) assessment in Amp-treated subjects subsequently revealed a gradual recovery of striatal dopamine function: FDOPA Ki values were decreased by approximately 70% at 1 month, approximately 45% at 6 months, approximately 20% at 12 months and were similar to pre-Amp values at 24 months. Motoric and social behavioral measures were obtained on all subjects within a species-typical group setting. Behavioral observations were conducted during both basal and stressor-challenge conditions, the latter being created by placing a potential intruder-animal in an individual cage adjacent to the subject's group enclosure. During basal conditions, post-Amp stereotypies were present at 2 weeks and locomotor behaviors were increased throughout 1 month; both alterations occurred while FDOPA Ki values were significantly decreased. Social behaviors were also significantly affected; affiliative behavior was decreased up to 6 months while aggressive behavior was increased for 12 months. However, a different pattern of behavioral changes emerged under stressor-challenge conditions. Motoric and social changes were of greater magnitude and persisted longer than in basal settings while aggressive behavior remained elevated at 24 months. These results indicate that chronic Amp-induced decreases in FDOPA Ki values and behavioral alterations are reversible. Changes in striatal dopamine function as indexed with FDOPA-PET are not correlated with post-Amp alterations in behaviors and moreover, expression of those behaviors is context-dependent.
采用为期10天的慢性苯丙胺（Amp）给药方案，以诱导黑长尾猴纹状体[18F]氟-L-多巴流入速率常数（FDOPA Ki）出现显著的长期下降。随后，对接受Amp治疗的受试者进行纵向FDOPA正电子发射断层扫描（PET）评估，结果显示纹状体多巴胺功能逐渐恢复：FDOPA Ki值在1个月时下降约70%，6个月时下降约45%，12个月时下降约20%，在24个月时与Amp给药前的值相似。在物种典型的群体环境中，对所有受试者进行运动和社会行为测量。在基础条件和应激源挑战条件下均进行行为观察，后者是通过将一只潜在的入侵动物放置在与受试者群体围栏相邻的单个笼子中产生的。在基础条件下，Amp给药后刻板行为在2周时出现，运动行为在整个1个月内增加；这两种改变均发生在FDOPA Ki值显著下降的同时。社会行为也受到显著影响；亲和行为在长达6个月的时间内减少，而攻击行为在12个月内增加。然而，在应激源挑战条件下出现了不同的行为变化模式。与基础环境相比，运动和社会变化的幅度更大且持续时间更长，而攻击行为在24个月时仍保持较高水平。这些结果表明，慢性Amp诱导的FDOPA Ki值下降和行为改变是可逆的。以FDOPA-PET为指标的纹状体多巴胺功能变化与Amp给药后的行为改变无关，而且，这些行为的表现取决于环境。
