Uchitomi Y, Yamawaki S
Department of Psychiatry & Neuroscience, Kure National Hospital, Japan.
Yakubutsu Seishin Kodo. 1987 Sep;7(3):383-92.
Effects of lithium, carbamazepine, zotepine, and clonazepam were examined on the behaviour mediated by 5-HT1A receptor and at 5-HT1A binding sites in rats. Forepaw treading, one component of 5-HT behavioural syndrome following subcutaneous injections of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), was not altered by reserpine, p-chlorophenylalanine, or alpha-methyl-p-tyrosine; in reserpine-treated rats, it was antagonized only by spiperone or by (-)-propranolol. These results indicate that 8-OH-DPAT-induced forepaw treading is produced by the direct stimulation of 5-HT1A receptor postsynaptically and also that this behaviour is not mediated by monoaminergic neurons. Lithium, carbamazepine, and zotepine inhibited forepaw treading in untreated rats; only lithium and clonazepam inhibited it in reserpine-treated rats. After 14 days treatment, only lithium enhanced it while its enhancement was abolished by reserpine. Radioligand binding studies using [3H]-8-OH-DPAT demonstrated that zotepine possessed weak affinity for 5-HT1A receptor; others lacked affinity. These results from acute experiments suggest that all drugs tested have inhibitory effects on the 5-HT1A receptor function. These effects, however, were not mediated by 5-HT1A receptor. And it is also suggested that the 5-HT1A receptor function after chronic lithium treatment might be enhanced by monoaminergic systems transsynaptically.
研究了锂盐、卡马西平、佐替平及氯硝西泮对大鼠5-HT1A受体介导行为及5-HT1A结合位点的影响。前爪踏地是皮下注射8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）后5-HT行为综合征的一个组成部分，利血平、对氯苯丙氨酸或α-甲基对酪氨酸对此无影响；在利血平处理的大鼠中，仅螺哌隆或（-）-普萘洛尔可拮抗该行为。这些结果表明，8-OH-DPAT诱导的前爪踏地是由5-HT1A受体的直接突触后刺激产生的，并且该行为不是由单胺能神经元介导的。锂盐、卡马西平和佐替平可抑制未处理大鼠的前爪踏地；在利血平处理的大鼠中，只有锂盐和氯硝西泮可抑制该行为。治疗14天后，只有锂盐可增强该行为，而利血平可消除其增强作用。使用[3H]-8-OH-DPAT进行的放射性配体结合研究表明，佐替平对5-HT1A受体具有弱亲和力；其他药物缺乏亲和力。急性实验的这些结果表明，所有测试药物对5-HT1A受体功能均有抑制作用。然而，这些作用不是由5-HT1A受体介导的。还表明，慢性锂治疗后5-HT1A受体功能可能通过单胺能系统经突触增强。
