INJECTION OF BICUCULLINE ELICITS FIRING OF LUTEINIZING-HORMONE-RELEASING HORMONE PULSE-GENERATOR IN MUSCIMOL-TREATED OVARIECTOMIZED RATS
INJECTION OF BICUCULLINE ELICITS FIRING OF LUTEINIZING-HORMONE-RELEASING HORMONE PULSE-GENERATOR IN MUSCIMOL-TREATED OVARIECTOMIZED RATS
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DOI：
10.1016/0006-8993(94)90145-7
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发表时间：
1994-04-04
期刊：
影响因子：
2.9
通讯作者：
KIMURA, F
中科院分区：
文献类型：
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作者：
HIRUMA, H;SANO, A;KIMURA, F
我们已经证明，尽管外源性γ -氨基丁酸(A) （GABA(A)）受体激动剂能够抑制促黄体生成素释放激素（LHRH）脉冲发生器的活性，但内源性GABA(A)受体活性的降低对去卵巢大鼠没有显著影响，这表明抑制性GABA神经元在控制LHRH脉冲释放中的作用很小。本研究通过记录去卵巢大鼠下丘脑的多单位活性（MUA），进一步分析GABA(A)受体系统对LHRH脉冲发生器活性的调控作用。弓形核(ARC)-中隆起区（ME）的MUA突然增加（齐射），同时伴有黄体生成素（LH）脉冲的启动，通过测量同时采集的血液中的LH浓度来确定。注射1 ~ 3 mg/kg GABA(a)受体激动剂muscimol （MUS）可降低基础MUA，延迟下一波MUA的发生，但未改变LH脉幅。在持续输注MUS （5 mg/kg/h）期间，静脉注射GABA(a)受体拮抗剂bicuculline (5 mg/kg)，降低了基础MUA，阻止了MUA截击的发生，诱发了MUA截击和LH脉冲，其振幅与输注MUS前相似。在生理盐水输注期间，注射相同剂量的BIC可短暂增加MUA，但这种增加不伴有LH脉冲，随后在常规间隔出现MUA截击，并伴有LH脉冲，但脉冲幅度不变。这些结果表明，GABA(A)受体活性抑制LHRH脉冲发生器活性，当GABA能活性极高时，GABA(A)受体活性的降低能够引起卵巢切除条件下LHRH脉冲发生器的激活。
We have already demonstrated that, although exogenous gamma-aminobutyric acid(A) (GABA(A)) receptor agonist is capable of inhibiting the activity of luteinizing hormone releasing hormone (LHRH) pulse generator, the reduction in the endogenous GABA(A) receptor activity does not have a significant effect in ovariectomized rats, suggesting a minor role of inhibitory GABA neurons in the control of pulsatile release of LHRH. In this study, we further analyzed the role of the GABA(A) receptor system in the regulation of LHRH pulse generator activity observed by recording the multiunit activity (MUA) in the hypothalamus of ovariectomized rats. An abrupt increase (volley) in the MUA in the arcuate nucleus (ARC)-median eminence region (ME) was accompanied by the initiation of a luteinizing hormone (LH) pulse, determined by measuring LH concentrations in blood sampled simultaneously. The injection of 1-3 mg/kg muscimol (MUS), a GABA(A) receptor agonist, decreased the basal MUA and delayed the occurrence of the next MUA volley, but it did not change the LH pulse amplitude. I.v. injection of 5 mg/kg bicuculline (BIC), a GABA(A) receptor antagonist, during continuous infusion of MUS (5 mg/kg/h) which decreased the basal MUA and prevented the MUA volley from occurring, evoked MUA volleys and LH pulses whose amplitudes were similar to those found before the MUS infusion. Injection of the same dose of BIC during the infusion of saline increased the MUA transiently, but this increase was not accompanied by an LH pulse and afterwards there occurred MUA volleys at ordinary intervals accompanied by LH pulses with unchanged pulse amplitudes. These results suggest that the GABA(A) receptor activity inhibits the LHRH pulse generator activity and that when the GABAergic activity is extremely high, a reduction in the GABA(A) receptor activity is able to cause activation of the LHRH pulse generator in the ovariectomized condition.