Effects of D-amphetamine and phencyclidine on behavior and extracellular concentrations of neurotensin and dopamine in the ventral striatum and the medial prefrontal cortex of the rat
Effects of D-amphetamine and phencyclidine on behavior and extracellular concentrations of neurotensin and dopamine in the ventral striatum and the medial prefrontal cortex of the rat
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DOI：
10.1016/0166-4328(96)00138-6
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发表时间：
1996-12-14
影响因子：
2.7
通讯作者：
Svensson, TH
中科院分区：
文献类型：
--
作者：
Hertel, P;Mathe, JM;Svensson, TH
采用微透析方法，研究了全身给药苯环利定（PCP; 2.5 mg/kg, s.c）和d -安非他明（1.5 mg/kg, s.c）对自由运动大鼠腹侧纹状体（vSTR）和内侧前额叶皮层（mPFC）神经紧张素样免疫反应性（NT-LI）和多巴胺（DA）细胞外浓度的影响。在单独的动物中，还分析了PCP和d -安非他明对开阔场地活动的影响。PCP，而非d -安非他明，导致vSTR中NT-LI水平显著增加（比基线增加156%），持续时间相对较短，即持续时间小于2小时。相比之下，两种药物在同一时期显著增加了mPFC中的NT-LI浓度，几乎增加了100%。PCP和d -安非他明也显著提高了vSTR细胞外DA水平，分别提高了83%和364%。而PCP对DA作用的峰值出现时间晚于d -安非他明，分别在给药后150 min和60 min。同样在mPFC中，PCP和d -安非他明分别显著增加DA浓度98%和284%。一般来说，PCP和d -安非他明对DA水平的影响与它们对NT-LI水平的影响相比，明显更持久，即持续时间为3-4小时。在行为上，d -安非他明比PCP产生更明显、更普遍的激活，激活的开始时间更快，即在给药后30分钟vs 90分钟。然而，这两种药物对大鼠行为活动的空间组织产生持久的影响，持续时间为3-4小时。综上所述，d -安非他明（1.5 mg/kg, s.c）比PCP （2.5 mg/kg, s.c）对大鼠的行为刺激更明显，这在很大程度上可以解释为其在大脑中更有效的da释放作用。PCP的初始行为抑制，如饲养，以及其一般较差的运动刺激作用，可能与vSTR中NT的释放有关。然而，PCP和d -安非他明造成的长期行为紊乱可能与中皮层DA释放增加有关，而不是与NT释放增加有关。
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.