Kaster Manuella P, Budni Josiane, Binfaré Ricardo W, Santos Adair R S, Rodrigues Ana Lúcia S
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário-Trindade-88040-900, Florianópolis-SC, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13;31(3):690-6. doi: 10.1016/j.pnpbp.2006.12.018. Epub 2007 Jan 12.
It was previously shown that the acute administration of adenosine elicits an antidepressant-like effect in the mouse forced swimming test (FST) by a mechanism dependent on the inhibition of the L-arginine-nitric oxide (NO)-guanylate cyclase pathway. Taken into account that the stimulation of this pathway is associated with the activation of K(+) channels, this study investigated the involvement of different types of K(+) channels in the effect of adenosine in the FST. Intracerebroventricular treatment of mice with tetraethylammonium (TEA, a non-specific inhibitor of K(+) channels, 25 pg/site), glibenclamide (an ATP-sensitive K(+) channel inhibitor, 0.5 pg/site), charybdotoxin (a large- and intermediate-conductance calcium-activated K(+) channel inhibitor, 25 pg/site) or apamin (a small-conductance calcium-activated K(+) channel inhibitor, 10 pg/site) was able to potentiate the action of subeffective doses of adenosine (1 mg/kg, i.p.) and fluoxetine (a serotonin reuptake inhibitor, 10 mg/kg, i.p.). Furthermore, the administration of adenosine or fluoxetine and the K(+) channel inhibitors, alone or in combination, did not affect the ambulatory behavior. Moreover, the reduction in the immobility time elicited by active doses of adenosine (10 mg/kg, i.p.) or fluoxetine (32 mg/kg, i.p.) in the FST was prevented by the pretreatment of mice with cromakalim (a K(+) channel opener, 10 microg/site, i.c.v.), without affecting the locomotion in an open-field. Together these results indicate that the modulatory effects of adenosine and fluoxetine on neuronal excitability, via inhibition of K(+) channels, may represent the final pathway of their antidepressant-like effects in the FST.
先前的研究表明，急性给予腺苷可通过依赖于抑制L-精氨酸-一氧化氮（NO）-鸟苷酸环化酶途径的机制，在小鼠强迫游泳试验（FST）中引发抗抑郁样效应。鉴于该途径的刺激与钾离子（K(+)）通道的激活相关，本研究调查了不同类型的K(+)通道在腺苷对FST作用中的参与情况。用四乙铵（TEA，一种K(+)通道的非特异性抑制剂，25 pg/位点）、格列本脲（一种ATP敏感性K(+)通道抑制剂，0.5 pg/位点）、蝎毒素（一种大电导和中电导钙激活K(+)通道抑制剂，25 pg/位点）或蜂毒明肽（一种小电导钙激活K(+)通道抑制剂，10 pg/位点）对小鼠进行脑室内处理，能够增强亚有效剂量的腺苷（1 mg/kg，腹腔注射）和氟西汀（一种5-羟色胺再摄取抑制剂，10 mg/kg，腹腔注射）的作用。此外，单独或联合给予腺苷、氟西汀和K(+)通道抑制剂，均不影响自主活动行为。而且，在FST中，用克罗卡林（一种K(+)通道开放剂，10 μg/位点，脑室内注射）预处理小鼠，可防止活性剂量的腺苷（10 mg/kg，腹腔注射）或氟西汀（32 mg/kg，腹腔注射）引起的不动时间减少，且不影响旷场试验中的运动能力。这些结果共同表明，腺苷和氟西汀通过抑制K(+)通道对神经元兴奋性的调节作用，可能代表了它们在FST中抗抑郁样效应的最终途径。
