Nomikos G G, Gruber S, Svensson T H, Mathé A A
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Eur Neuropsychopharmacol. 2000 Dec;10(6):495-500. doi: 10.1016/s0924-977x(00)00122-x.
The effects of acute and chronic electroconvulsive stimuli (ECS) on extracellular concentrations of the cyclic nucleotides, cAMP and cGMP, from the striatum and hippocampus of awake rats were studied with in vivo microdialysis in conjunction with radioimmunoassay. Acute ECS, but not acute sham-ECS, significantly increased cAMP and cGMP efflux from the striatum by about 75 and 50%, respectively. Chronic ECS did not influence significantly basal efflux of cAMP or cGMP from the striatum or the hippocampus in comparison to control animals receiving chronically sham-ECS. Administration of a challenge ECS in animals treated chronically with sham-ECS resulted in an increase in cAMP and cGMP concentrations in the striatum by 20%, but it failed to affect significantly efflux of these nucleotides in animals treated chronically with ECS. Similarly, in the hippocampus, administration of a challenge ECS in animals treated chronically with sham-ECS resulted in an increase in cAMP and cGMP concentrations by about 40 and 65%, respectively, whereas it failed to affect significantly efflux of these nucleotides in animals treated chronically with ECS. Thus, acutely administered ECS increases cAMP and cGMP efflux in the striatum and hippocampus of rats, an effect that is greatly diminished in animals chronically receiving ECS. These findings suggest changes in the cAMP and cGMP signal transduction mechanisms in response to acute and chronic ECS that may be related to the therapeutic effects of this antidepressant and antipsychotic treatment.
采用体内微透析结合放射免疫分析法,研究了急性和慢性电惊厥刺激(ECS)对清醒大鼠纹状体和海马中环核苷酸cAMP和cGMP细胞外浓度的影响。急性ECS而非急性假ECS显著增加了纹状体中cAMP和cGMP的流出,分别增加了约75%和50%。与长期接受假ECS的对照动物相比,慢性ECS对纹状体或海马中cAMP或cGMP的基础流出没有显著影响。在长期接受假ECS治疗的动物中给予一次激发性ECS,可使纹状体中cAMP和cGMP浓度增加20%,但对长期接受ECS治疗的动物中这些核苷酸的流出没有显著影响。同样,在海马中,在长期接受假ECS治疗的动物中给予一次激发性ECS,可使cAMP和cGMP浓度分别增加约40%和65%,而对长期接受ECS治疗的动物中这些核苷酸的流出没有显著影响。因此,急性给予ECS可增加大鼠纹状体和海马中cAMP和cGMP的流出,而在长期接受ECS的动物中这种作用大大减弱。这些发现提示了cAMP和cGMP信号转导机制在急性和慢性ECS作用下的变化,这可能与这种抗抑郁和抗精神病治疗的疗效有关。