Freo U, Pietrini P, Pizzolato G, Furey-Kurkjian M, Merico A, Ruggero S, Dam M, Battistin L
Clinica delle Malattie Nervose e Mentali, Padova, Italy.
Brain Res. 1995 Apr 24;677(2):213-20. doi: 10.1016/0006-8993(95)00140-l.
In this study we compared the effects of the anxiolytic buspirone on behavior and regional cerebral metabolic rates for glucose (rCMRglc) with those of the reference serotonin (5-HT)1A agonist 8-hydroxy-2(di-N-propylamino)tetralin (DPAT). Behavioral effects were assessed by scoring the 5-HT syndrome. rCMRglc was measured in 56 brain regions by using the quantitative autoradiographic [14C]2-deoxyglucose technique, at 10 min after i.p. injection of DPAT (1 mg/kg) or buspirone (0.4, 4 and 40 mg/kg) in awake male Fischer-344 rats. Whereas DPAT produced an intense 5-HT syndrome, buspirone had no behavioral effect. A low dose (0.4 mg/kg) of buspirone reduced rCMRglc in 18 brain areas (32%), more markedly in limbic areas and raphe nuclei. These were the only rCMRglc effects buspirone had in common with the potent 5-HT1A agonist DPAT and suggest that low dose buspirone activates preferentially 5-HT1A receptors. Hence, this receptor subtype may mediate buspirone functional effects on the limbic system and, given the role of these brain areas in mood control, possibly buspirone therapeutic actions. High doses (4 and 40 mg/kg) of buspirone produced widespread rCMRglc decreases in 46 (82%) and 44 (79%) of the areas studied and increased rCMRglc in one brain area, the lateral habenula, that was not affected by DPAT or a low dose of buspirone. The topographic distribution and direction of rCMRglc changes by high doses of buspirone differ from those produced by the 5-HT1A agonist DPAT. Instead these changes resemble the rCMRglc effects of dopaminergic D2 antagonists like haloperidol and are consistent with some pharmacological and binding properties of buspirone.(ABSTRACT TRUNCATED AT 250 WORDS)
在本研究中，我们比较了抗焦虑药丁螺环酮与参比血清素（5-HT）1A激动剂8-羟基-2-（二-N-丙基氨基）四氢萘（DPAT）对行为和局部脑葡萄糖代谢率（rCMRglc）的影响。通过对5-HT综合征进行评分来评估行为效应。采用定量放射自显影[14C]2-脱氧葡萄糖技术，在清醒雄性Fischer-344大鼠腹腔注射DPAT（1mg/kg）或丁螺环酮（0.4、4和40mg/kg）10分钟后，测量56个脑区的rCMRglc。DPAT引发强烈的5-HT综合征，而丁螺环酮无行为效应。低剂量（0.4mg/kg）丁螺环酮使18个脑区（32%）的rCMRglc降低，在边缘区和中缝核更为明显。这些是丁螺环酮与强效5-HT1A激动剂DPAT共有的仅有的rCMRglc效应，表明低剂量丁螺环酮优先激活5-HT1A受体。因此，该受体亚型可能介导丁螺环酮对边缘系统的功能效应，鉴于这些脑区在情绪控制中的作用，也可能介导丁螺环酮的治疗作用。高剂量（4和40mg/kg）丁螺环酮使所研究的46个（82%）和44个（79%）脑区的rCMRglc普遍降低，并使一个脑区（外侧缰核）的rCMRglc升高，该脑区不受DPAT或低剂量丁螺环酮的影响。高剂量丁螺环酮引起的rCMRglc变化的地形图分布和方向与5-HT1A激动剂DPAT产生的不同。相反，这些变化类似于多巴胺能D2拮抗剂（如氟哌啶醇）的rCMRglc效应，并且与丁螺环酮的一些药理学和结合特性一致。（摘要截短于250字）
