关键词: L-type calcium channel T-type calcium channel defensive behaviors mibefradil periaqueductal gray matter verapamil

Mesh : Animals Periaqueductal Gray / drug effects physiology Male Calcium Channels, T-Type / physiology drug effects metabolism Calcium Channels, L-Type / metabolism Calcium Channel Blockers / pharmacology Mibefradil / pharmacology Verapamil / pharmacology Electric Stimulation Rats Rats, Wistar Microinjections Dose-Response Relationship, Drug

来  源:   DOI:10.1016/j.neuropharm.2024.110059

Abstract:
Stimulation of the dorsal half of the rat periaqueductal gray (DPAG) with 60-Hz pulses of increasing intensity, 30-μA pulses of increasing frequency, or increasing doses of an excitatory amino acid elicits sequential defensive responses of exophthalmia, immobility, trotting, galloping, and jumping. These responses may be controlled by voltage-gated calcium channel-specific firing patterns. Indeed, a previous study showed that microinjection of the DPAG with 15 nmol of verapamil, a putative blocker of L-type calcium channels, attenuated all defensive responses to electrical stimulation at the same site as the injection. Accordingly, here we investigated the effects of microinjection of lower doses (0.7 and 7 nmol) of both verapamil and mibefradil, a preferential blocker of T-type calcium channels, on DPAG-evoked defensive behaviors of the male rat. Behaviors were recorded either 24 h before or 10 min, 24 h, and 48 h after microinjection. Effects were analyzed by both threshold logistic analysis and repeated measures analysis of variance for treatment by session interactions. Data showed that the electrodes were all located within the dorsolateral PAG. Compared to the effects of saline, verapamil significantly attenuated exophthalmia, immobility, and trotting. Mibefradil significantly attenuated exophthalmia and marginally attenuated immobility while facilitating trotting. While galloping was not attenuated by either antagonist, jumping was unexpectedly attenuated by 0.7 nmol verapamil only. These results suggest that T-type calcium channels are involved in the low-threshold freezing responses of exophthalmia and immobility, whereas L-type calcium channels are involved in the trotting response that precedes the full-fledged escape responses of galloping and jumping.
摘要:
用60Hz强度增加的脉冲刺激大鼠导水管周围灰质(DPAG)的背侧一半,增加频率的30μA脉冲,或增加兴奋性氨基酸的剂量会引起眼球突出的顺序防御反应,不动,小跑,疾驰,和跳跃。这些反应可以通过电压门控钙通道特异性放电模式来控制。的确,先前的一项研究表明,用15nmol的维拉帕米显微注射DPAG,一种推定的L型钙通道阻滞剂,在与注射相同的部位减弱了对电刺激的所有防御反应。因此,在这里,我们研究了低剂量(0.7和7nmol)的维拉帕米和米贝拉迪尔的显微注射的效果,T型钙通道的优先阻断剂,雄性大鼠DPAG诱发的防御行为。行为记录前24小时或10分钟,24h,和显微注射后48小时。通过阈值逻辑分析和重复测量方差分析对治疗的影响进行了分析。数据显示电极均位于背外侧PAG内。与盐水的作用相比,维拉帕米显著减轻眼球突出症,不动,和小跑。Mibefradil可显着减轻眼球突出症,并在促进小跑的同时略微减轻了不动。虽然两种拮抗剂都没有减弱舞步,只有0.7nmol维拉帕米意外地减弱了跳跃。这些结果表明,T型钙通道参与了眼球突出和不动的低阈值冻结反应,而L型钙通道参与小跑反应,先于跑动和跳跃的全面逃逸反应。
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