Bjorvatn B, Fornal C A, Martín F J, Metzler C W, Jacobs B L
Department of Psychology, Princeton University, NJ, USA.
Eur J Pharmacol. 1998 Sep 4;356(2-3):167-78. doi: 10.1016/s0014-2999(98)00530-5.
The effects of the putative 5-HT1A receptor antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzam ide (p-MPPI) were examined on the activity of serotonergic dorsal raphe nucleus neurons in freely moving cats. Systemic administration of p-MPPI produced a dose-dependent increase in firing rate. This stimulatory effect of p-MPPI was evident during wakefulness (when serotonergic neurons display a relatively high level of activity), but not during sleep (when serotonergic neurons display little or no spontaneous activity). p-MPPI also blocked the ability of the 5-HT1A receptor agonist 8-hydroxy-(2-di-n-propylamino)tetralin (8-OH-DPAT) to inhibit serotonergic neuronal activity. This antagonism was evident both as a reversal of the neuronal inhibition produced by prior injection of 8-OH-DPAT and as a shift in the potency of 8-OH-DPAT following p-MPPI pretreatment. Overall, these results in behaving animals indicate that p-MPPI acts as an effective 5-HT1A autoreceptor antagonist. The increase in firing rate produced by p-MPPI supports the hypothesis that autoreceptor-mediated feedback inhibition operates under physiological conditions.
研究了假定的5-羟色胺1A（5-HT1A）受体拮抗剂4-碘-N-[2-[4-(甲氧基苯基)-1-哌嗪基]乙基]-N-2-吡啶基苯甲酰胺（p-MPPI）对自由活动猫中血清素能背缝核神经元活性的影响。全身给予p-MPPI会使放电率呈剂量依赖性增加。p-MPPI的这种刺激作用在清醒状态下（此时血清素能神经元表现出相对较高的活性水平）很明显，但在睡眠状态下（此时血清素能神经元几乎没有或没有自发活动）则不明显。p-MPPI还阻断了5-HT1A受体激动剂8-羟基-（2-二正丙基氨基）四氢萘（8-OH-DPAT）抑制血清素能神经元活性的能力。这种拮抗作用既表现为对先前注射8-OH-DPAT所产生的神经元抑制的逆转，也表现为p-MPPI预处理后8-OH-DPAT效力的改变。总体而言，这些在行为动物身上的结果表明p-MPPI作为一种有效的5-HT1A自身受体拮抗剂发挥作用。p-MPPI所产生的放电率增加支持了自身受体介导的反馈抑制在生理条件下起作用的假说。
