Jäkälä P, Björklund M, Riekkinen P
Department of Neurology, University of Kuopio, Finland.
Eur J Pharmacol. 1996 Mar 28;299(1-3):47-60. doi: 10.1016/0014-2999(95)00833-0.
To investigate the roles of the nicotinic acetylcholine receptor and the serotonin (5-hydroxytryptamine; 5-HT) subtype 2 receptor in the modulation of rat thalamocortical oscillations, the effects of systemic (s.c.) administration of nicotine, a nicotinic acetylcholine receptor agonist, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 receptor agonist, on neocortical high-voltage spindle activity occurring during quiet waking-immobility behavior in aged (28 months of age) and adult (7 months of age) rats were studied. Nicotine 0.1 and 0.3 mg/kg alleviated the age-related increase of neocortical high-voltage spindles, whereas in adult rats only nicotine 0.3 mg/kg was effective. DOI 0.3, 1.0 and 2.0 mg/kg suppressed high-voltage spindles in both aged and adult rats. In aged rats, a combination of subthreshold doses of nicotine (0.03 mg/kg) and DOI (0.1 mg/kg) decreased neocortical high-voltage spindles, whereas in adult rats two different subthreshold dose combinations (nicotine 0.03 or 0.1 mg/kg+DOI 0.1 mg/kg) had no effect. p-Chlorophenylalanine (400 mg/kg/day i.p. for 3 consecutive days) treatment decreased brain serotonin concentration (> 80% reduction), but did not affect high-voltage spindles. However, in both aged and adult rats, p-chlorophenylalanine treatment blocked the decrease in high-voltage spindle activity produced by DOI 0.3 mg/kg, though not the decrease produced by higher doses of DOI (1.0 and 2.0 mg/kg). It is important that, in adult rats, p-chlorophenylalanine treatment was able to abolish the decrease in high-voltage spindle activity seen after a relatively high dose of nicotine (0.3 mg/kg). The results suggest that nicotinic acetylcholine and 5-HT2 receptors may act in concert to suppress neocortical high-voltage spindling in rats, and that intact brain serotonergic systems may be important for some of the therapeutic effects of nicotine.
为研究烟碱型乙酰胆碱受体和5-羟色胺（5-羟色胺；5-HT）2型受体在调节大鼠丘脑皮质振荡中的作用，我们研究了全身（皮下）给予烟碱型乙酰胆碱受体激动剂烟碱以及5-HT2受体激动剂1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI）对老年（28月龄）和成年（7月龄）大鼠安静觉醒-静止行为期间新皮质高压纺锤波活动的影响。0.1和0.3mg/kg的烟碱减轻了新皮质高压纺锤波与年龄相关的增加，而在成年大鼠中只有0.3mg/kg的烟碱有效。0.3、1.0和2.0mg/kg的DOI抑制了老年和成年大鼠的高压纺锤波。在老年大鼠中，阈下剂量的烟碱（0.03mg/kg）和DOI（0.1mg/kg）联合使用可减少新皮质高压纺锤波，而在成年大鼠中，两种不同的阈下剂量组合（烟碱0.03或0.1mg/kg+DOI 0.1mg/kg）则没有效果。对氯苯丙氨酸（400mg/kg/天，腹腔注射，连续3天）治疗降低了脑内5-羟色胺浓度（降低>80%），但不影响高压纺锤波。然而，在老年和成年大鼠中，对氯苯丙氨酸治疗均阻断了0.3mg/kg DOI引起的高压纺锤波活动降低，但未阻断更高剂量DOI（1.0和2.0mg/kg）引起的降低。重要的是，在成年大鼠中，对氯苯丙氨酸治疗能够消除相对高剂量烟碱（0.3mg/kg）后出现的高压纺锤波活动降低。结果表明，烟碱型乙酰胆碱受体和5-HT2受体可能协同作用以抑制大鼠新皮质高压纺锤波，并且完整的脑5-羟色胺能系统对于烟碱的某些治疗作用可能很重要。
