Jäkälä P, Riekkinen P
Department of Neuroscience and Neurology, University of Kuopio, Finland.
Pharmacol Biochem Behav. 1997 Apr;56(4):713-8. doi: 10.1016/s0091-3057(96)00411-x.
The present study investigated whether combined stimulation of the cholinergic system and 5-hydroxytryptamine (5-HT) subtype 2 receptors can suppress neocortical high-voltage spindles (HVSs) reflecting thalamocortical oscillations in aged rats. Cholinesterase inhibitors-tetrahydro-aminoacridine (THA: 1.0 and 3.0 mg/kg i.p.) and physostigmine (0.36 mg/kg i.p.)- and a 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 0.3 and 1.0 mg/kg SC)-suppressed HVSs in aged rats. A combination of subthreshold doses of THA (0.3 mg/kg i.p.) and DOI (0.1 mg/kg s.c.) suppressed HVSs more effectively than either drug alone. Furthermore, a 5-HT2 receptor antagonist, ketanserin (5.0 and 20.0 mg/kg s.c.), reduced the efficacy of THA (1.0 and 3.0 mg/kg i.p.) and physostigmine (0.12 and 0.36 mg/kg i.p.) in decreasing HVSs. THA and ketanserin slightly decreased, physostigmine tended to increase, and DOI significantly increased behavioral activity of the rats, demonstrating that the effects of the drugs on behavioral activity may be separated from their effects on generation of thalamocortical oscillations. The results suggest that activation of the cholinergic system and 5-HT2 receptors has additive effects in the suppression of thalamocortical oscillations in aged rats.
本研究调查了胆碱能系统与5-羟色胺（5-HT）2型受体的联合刺激是否能抑制反映老年大鼠丘脑皮质振荡的新皮质高电压纺锤波（HVSs）。胆碱酯酶抑制剂——四氢氨基吖啶（THA：腹腔注射1.0和3.0mg/kg）和毒扁豆碱（腹腔注射0.36mg/kg）——以及5-HT2受体激动剂1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI；皮下注射0.3和1.0mg/kg）可抑制老年大鼠的HVSs。阈下剂量的THA（腹腔注射0.3mg/kg）和DOI（皮下注射0.1mg/kg）联合使用比单独使用任何一种药物更有效地抑制了HVSs。此外，5-HT2受体拮抗剂酮色林（皮下注射5.0和20.0mg/kg）降低了THA（腹腔注射1.0和3.0mg/kg）和毒扁豆碱（腹腔注射0.12和0.36mg/kg）降低HVSs的效果。THA和酮色林略微降低了大鼠的行为活动，毒扁豆碱有增加行为活动的趋势，而DOI显著增加了大鼠的行为活动，这表明药物对行为活动的影响可能与其对丘脑皮质振荡产生的影响相分离。结果表明，胆碱能系统和5-HT2受体的激活在抑制老年大鼠丘脑皮质振荡方面具有相加作用。
