Jäkälä P, Björklund M, Koivisto E, Riekkinen P
Department of Neurology, University of Kuopio, Finland.
Eur J Pharmacol. 1996 Dec 5;316(2-3):181-93. doi: 10.1016/s0014-2999(96)00679-6.
To investigate the roles of the cholinergic system and 5-HT2 receptors in the modulation of thalamocortical oscillations, we studied the effects of systemic (s.c.) administration of anticholinesterases (physostigmine, tetrahydroaminoacridine) and muscarinic acetylcholine receptor agonists (pilocarpine, oxotremorine) on spontaneous thalamically generated rhythmic neocortical high-voltage spindles in adult rats pretreated with either saline or ketanserin, a 5-HT2 receptor antagonist. Ketanserin at 20.0 mg/kg increased the number of high-voltage spindles. In saline-treated rats, tetrahydroaminoacridine 3.0 and 9.0 mg/kg was able to decrease high-voltage spindles, whereas in ketanserin 20.0 mg/kg-treated rats only the highest dose of tetrahydroaminoacridine (9.0 mg/kg) decreased high-voltage spindles. Both doses of physostigmine, 0.12 and 0.36 mg/kg, decreased high-voltage spindles in both saline and ketanserin 20.0 mg/kg-treated rats. Lower doses of tetrahydroaminoacridine (1.0 mg/kg) and physostigmine (0.06 mg/kg) were ineffective in both saline- and ketanserin 20.0 mg/kg-treated rats. Pilocarpine 3.0 mg/kg and oxotremorine 0.1 and 0.9 mg/kg decreased high-voltage spindles in saline-treated rats. However, in rats treated with ketanserin 20.0 mg/kg, only the lower doses of pilocarpine (0.3 and 1.0 mg/kg) and oxotremorine (0.03 mg/kg) were able to decrease the high-voltage spindles. The results suggest that activation of the cholinergic system and activation of 5-HT2 receptors have additive effects in the suppression of thalamocortical oscillations and related neocortical high-voltage spindles in rats, thus maintaining effective information processing in thalamocortical networks.
为了研究胆碱能系统和5-HT2受体在丘脑皮质振荡调节中的作用，我们研究了全身（皮下）给予抗胆碱酯酶药（毒扁豆碱、他克林）和毒蕈碱型乙酰胆碱受体激动剂（毛果芸香碱、氧化震颤素）对成年大鼠自发性丘脑产生的节律性新皮质高电压纺锤波的影响，这些大鼠预先注射了生理盐水或5-HT2受体拮抗剂酮色林。20.0mg/kg的酮色林增加了高电压纺锤波的数量。在生理盐水处理的大鼠中，3.0mg/kg和9.0mg/kg的他克林能够减少高电压纺锤波，而在20.0mg/kg酮色林处理的大鼠中，只有最高剂量的他克林（9.0mg/kg）能减少高电压纺锤波。0.12mg/kg和0.36mg/kg的毒扁豆碱剂量在生理盐水和20.0mg/kg酮色林处理的大鼠中均能减少高电压纺锤波。较低剂量的他克林（1.0mg/kg）和毒扁豆碱（0.06mg/kg）在生理盐水和20.0mg/kg酮色林处理的大鼠中均无效。3.0mg/kg的毛果芸香碱和0.1mg/kg及0.9mg/kg的氧化震颤素在生理盐水处理的大鼠中减少了高电压纺锤波。然而，在20.0mg/kg酮色林处理的大鼠中，只有较低剂量的毛果芸香碱（0.3mg/kg和1.0mg/kg）和氧化震颤素（0.03mg/kg）能够减少高电压纺锤波。结果表明，胆碱能系统的激活和5-HT2受体的激活在抑制大鼠丘脑皮质振荡及相关新皮质高电压纺锤波方面具有相加作用，从而维持丘脑皮质网络中的有效信息处理。
