Hertel P, Mathé J M, Nomikos G G, Iurlo M, Mathé A A, Svensson T H
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Behav Brain Res. 1995 Dec 14;72(1-2):103-14. doi: 10.1016/0166-4328(96)00138-6.
The effects of systemically administered phencyclidine (PCP; 2.5 mg/kg, s.c.) and D-amphetamine (1.5 mg/kg, s.c.) on the extracellular concentrations of neurotensin-like immunoreactivity (NT-LI) and dopamine (DA) in the ventral striatum (vSTR) and the medial prefrontal cortex (mPFC) were studied in freely moving rats using microdialysis. In separate animals, the effects of PCP and D-amphetamine on open field activity were also analyzed. PCP, but not D-amphetamine, caused a significant increase (156% over baseline) of NT-LI levels in the vSTR which was relatively short lasting, i.e., of less than 2 h duration. In contrast, both drugs significantly increased NT-LI concentrations in the mPFC by almost 100% during the same period. PCP and D-amphetamine also significantly increased extracellular levels of DA in the vSTR by 83 and 364%, respectively. However, the peak effect of PCP on DA appeared later than that of D-amphetamine, i.e., at 150 and 60 min, respectively, after drug administration. Also in the mPFC, both PCP and D-amphetamine significantly increased DA concentrations by 98 and 284%, respectively. Generally, effects on DA levels of both PCP and D-amphetamine were, in contrast to their effects on NT-LI levels, clearly more long-lasting, i.e., of 3-4 h duration. Behaviorally, D-amphetamine produced a more pronounced, general activation than PCP, with a faster onset of activation, i.e. within 30 vs 90 min after administration. However, both drugs produced long-lasting effects on the spatial organization of behavioral activity, which lasted for 3-4 h. In conclusion, the more pronounced behavioral stimulation by D-amphetamine (1.5 mg/kg, s.c.) vs PCP (2.5 mg/kg, s.c.) in the rat may largely be explained by its more potent DA-releasing effect in the brain. Initial behavioral suppression by PCP, e.g., of rearing, as well as its rather poor locomotor stimulant action in general, might relate to release of NT in the vSTR. The long-lasting, behavioral disorganization by both PCP and D-amphetamine may, however, be related to increased release of DA rather than NT in the mesolimbocortical areas.
采用微透析技术，研究了系统给予苯环利定（PCP；2.5毫克/千克，皮下注射）和右旋苯丙胺（1.5毫克/千克，皮下注射）对自由活动大鼠腹侧纹状体（vSTR）和内侧前额叶皮质（mPFC）中神经降压素样免疫反应性（NT-LI）和多巴胺（DA）细胞外浓度的影响。在另外的动物中，还分析了PCP和右旋苯丙胺对旷场活动的影响。PCP而非右旋苯丙胺导致vSTR中NT-LI水平显著升高（比基线高156%），且持续时间相对较短，即不到2小时。相比之下，在同一时期，两种药物均使mPFC中的NT-LI浓度显著升高近100%。PCP和右旋苯丙胺还分别使vSTR中DA的细胞外水平显著升高83%和364%。然而，PCP对DA的峰值效应出现时间晚于右旋苯丙胺，分别在给药后150分钟和60分钟出现。同样在mPFC中，PCP和右旋苯丙胺分别使DA浓度显著升高98%和284%。一般来说，与它们对NT-LI水平的影响相比，PCP和右旋苯丙胺对DA水平的影响明显更持久，即持续3 - 4小时。行为学上，右旋苯丙胺比PCP产生更明显的全身激活作用，激活起效更快，即给药后30分钟对90分钟。然而，两种药物对行为活动的空间组织都产生了持久影响，持续3 - 4小时。总之，大鼠中右旋苯丙胺（1.5毫克/千克，皮下注射）比PCP（2.5毫克/千克，皮下注射）更明显的行为刺激作用可能很大程度上归因于其在脑中更强的DA释放效应。PCP最初的行为抑制作用，如对竖毛行为的抑制，以及其总体上相当弱的运动刺激作用，可能与vSTR中NT的释放有关。然而，PCP和右旋苯丙胺导致的持久行为紊乱可能与中脑边缘皮质区域中DA而非NT的释放增加有关。
