Rosen J B, Berman R F
Department of Psychology, Wayne State University, Detroit, Michigan.
Epilepsia. 1987 Nov-Dec;28(6):658-66. doi: 10.1111/j.1528-1157.1987.tb03697.x.
This study explored the anticonvulsant effects of adenosine analogs at the focus of seizures kindled from various brain structures. Chemitrodes were implanted in the amygdala (AM), hippocampus (HIPP), or caudate nucleus (CN) of Long-Evans rats and electrically stimulated once daily until fully generalized seizures appeared (i.e., kindled). Once kindled, various doses (0.001-0.5 microgram/0.5 microliter) of the adenosine analogs, L-phenylisopropyladenosine (L-PIA), N-ethylcarboximidoadenosine (NECA) or vehicle were injected into the seizure focus 5 min prior to electrical stimulation. The afterdischarge (AD) and behavioral seizure stages were measured. L-PIA had potent anticonvulsant effects when injected directly into the kindled seizure focus in the AM, HIPP, or CN. NECA effects were statistically significant only in CN-kindled seizures. The regional differences in efficacy of the two adenosine analogs suggest that L-PIA, an A1 adenosine subtype agonist, may exert its effects through A1 adenosine receptors in the AM, HIPP, and CN, where A1 binding has been demonstrated, whereas NECA, an A2 adenosine receptor agonist, may only be maximally effective in the CN where A2 adenosine binding sites are located.
本研究探讨了腺苷类似物在由各种脑结构引发的癫痫病灶处的抗惊厥作用。将化学微电极植入Long-Evans大鼠的杏仁核（AM）、海马体（HIPP）或尾状核（CN），每天进行一次电刺激，直至出现完全全身性癫痫发作（即点燃）。一旦点燃，在电刺激前5分钟将各种剂量（0.001 - 0.5微克/0.5微升）的腺苷类似物、L-苯基异丙基腺苷（L-PIA）、N-乙基羧基咪唑腺苷（NECA）或赋形剂注入癫痫病灶。测量后放电（AD）和行为性癫痫发作阶段。当直接注入AM、HIPP或CN的点燃癫痫病灶时，L-PIA具有强大的抗惊厥作用。NECA的作用仅在CN点燃的癫痫发作中具有统计学意义。两种腺苷类似物疗效的区域差异表明，A1腺苷亚型激动剂L-PIA可能通过AM、HIPP和CN中的A1腺苷受体发挥作用，在这些部位已证实存在A1结合，而A2腺苷受体激动剂NECA可能仅在存在A2腺苷结合位点的CN中发挥最大作用。
