Krebs-Thomson K, Lehmann-Masten V, Naiem S, Paulus M P, Geyer M A
Department of Psychiatry, University of California at San Diego, La Jolla 92093-0804, USA.
Eur J Pharmacol. 1998 Feb 19;343(2-3):135-43. doi: 10.1016/s0014-2999(97)01557-4.
To test the hypothesis that serotonergic modulation of the effects of phencyclidine (PCP) are due to circuit- rather than receptor-based interactions between glutamatergic and serotonergic systems, multivariate profiles of rat behavior were assessed after treatments with the 5-hydroxytryptamine (5-HT) 5-HT2 receptor antagonist ketanserin (1.0 mg/kg), the 5-HT2 receptor agonist (1(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) (DOI; 0.27 mg/kg), various doses of PCP (0.75 to 10.125 mg/kg), or combinations thereof. Ketanserin blocked all effects of DOI, but reduced the effects of PCP only on locomotion. Depending on the dose, PCP was observed to increase or decrease locomotion and the roughness of the rats' patterns of locomotion. In any case, DOI always increased the activity and decreased the roughness of locomotor paths in PCP-treated rats. Thus, co-administration of DOI and PCP did not yield a shift in the dose-effect curve for either drug, but instead resulted in a new behavioral profile consistent with a circuit-based dynamic interaction.
苯环己哌啶（PCP）作用的5-羟色胺能调节是由于谷氨酸能和5-羟色胺能系统之间基于回路而非受体的相互作用，在用5-羟色胺（5-HT）5-HT2受体拮抗剂酮色林（1.0毫克/千克）、5-HT2受体激动剂（1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷）（DOI；0.27毫克/千克）、不同剂量的PCP（0.75至10.125毫克/千克）或它们的组合进行处理后，评估了大鼠行为的多变量概况。酮色林阻断了DOI的所有作用，但仅降低了PCP对运动的影响。根据剂量不同，观察到PCP可增加或减少运动以及大鼠运动模式的粗糙程度。在任何情况下，DOI总是增加PCP处理大鼠的活动并降低运动路径的粗糙程度。因此，DOI和PCP联合给药并未使两种药物的剂量效应曲线发生偏移，而是产生了一种与基于回路的动态相互作用一致的新行为概况。
