Gur Eitan, Dremencov Eliyahu, Garcia Francisca, Van de Kar Louis D, Lerer Bernard, Newman Michael E
Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Brain Res. 2002 Oct 11;952(1):52-60. doi: 10.1016/s0006-8993(02)03193-1.
The aims of this work were to determine the influence of chronic electroconvulsive shock (ECS) on presynaptic 5-HT(1A) receptor function, postsynaptic 5-HT(1A) receptor function in hippocampus and hypothalamus, and presynaptic 5-HT(1B) receptor function in hippocampus and hypothalamus. This represents part of an on-going study of the effects of ECS on serotonergic receptor activity in selected brain areas which may be relevant to the effects of electroconvulsive therapy (ECT) in humans. Chronic ECS reduced the ability of the 5-HT(1A) receptor agonist 8-hydroxy-2(di-n-propylamino)tetraline (8-OH-DPAT) (0.2 mg/kg s.c.) to decrease 5-HT levels in hypothalamus as shown by in vivo microdialysis, indicative of a reduction in sensitivity of presynaptic 5-HT(1A) autoreceptors. The ability of the 5-HT(1B) receptor antagonist GR 127935 (5 mg/kg s.c.) to increase 5-HT levels in both hippocampus and hypothalamus was unaffected by chronic ECS. 8-OH-DPAT (0.2 mg/kg s.c.) increased cyclic AMP levels in hippocampus measured by in vivo microdialysis approximately 2-fold. The degree of stimulation of cyclic AMP formation was not altered by chronic ECS. However the cyclic AMP response to forskolin (50 micro M) administered via the microdialysis probe, which was approximately 4-fold of basal in sham-treated rats, was almost completely abolished in ECS-treated rats. Since this indicates that either adenylate cyclase catalytic unit activity or Gs protein activity is reduced in the hippocampus after chronic ECS, the lack of change in 8-OH-DPAT-induced cyclic AMP formation may be taken as possible evidence of an increase in sensitivity of postsynaptic 5-HT(1A) receptors in the hippocampus by chronic ECS. Chronic ECS increased basal plasma levels of corticosterone, ACTH and oxytocin. The ACTH response to s.c. injections of 0.2 mg/kg or 0.5 mg/kg 8-OH-DPAT was reduced by chronic ECS. Postsynaptic 5-HT(1A) receptor activity in the hypothalamus, in contrast to the hippocampus, thus appears to be desensitized after chronic ECS. We conclude that chronic ECS has regionally specific effects on both pre- and post-synaptic 5-HT(1A) receptors, but, in contrast to some antidepressant drugs, does not affect presynaptic 5-HT(1B) receptor activity.
本研究旨在确定慢性电惊厥休克（ECS）对海马体和下丘脑的突触前5-羟色胺（5-HT）1A受体功能、突触后5-HT1A受体功能以及海马体和下丘脑的突触前5-HT1B受体功能的影响。这是正在进行的关于ECS对特定脑区5-羟色胺能受体活性影响研究的一部分，这些脑区可能与人类电惊厥治疗（ECT）的效果相关。慢性ECS降低了5-HT1A受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）（0.2mg/kg皮下注射）通过体内微透析降低下丘脑5-羟色胺水平的能力，这表明突触前5-HT1A自身受体的敏感性降低。5-HT1B受体拮抗剂GR 127935（5mg/kg皮下注射）增加海马体和下丘脑5-羟色胺水平的能力不受慢性ECS的影响。8-OH-DPAT（0.2mg/kg皮下注射）通过体内微透析使海马体中环磷酸腺苷（cAMP）水平增加约2倍。慢性ECS并未改变cAMP形成的刺激程度。然而，通过微透析探针给予福斯高林（50μM）后，假手术组大鼠的cAMP反应约为基础水平的4倍，而在接受ECS治疗的大鼠中几乎完全消失。由于这表明慢性ECS后海马体中腺苷酸环化酶催化单位活性或Gs蛋白活性降低，8-OH-DPAT诱导的cAMP形成缺乏变化可能被视为慢性ECS使海马体中突触后5-HT1A受体敏感性增加的可能证据。慢性ECS增加了皮质酮、促肾上腺皮质激素（ACTH）和催产素的基础血浆水平。慢性ECS降低了皮下注射0.2mg/kg或0.5mg/kg 8-OH-DPAT后ACTH的反应。与海马体相反，慢性ECS后下丘脑的突触后5-HT1A受体活性似乎脱敏。我们得出结论，慢性ECS对突触前和突触后5-HT1A受体具有区域特异性影响，但与某些抗抑郁药物不同，它不影响突触前5-HT1B受体活性。
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