Pericić Danka
Laboratory for Molecular Neuropharmacology, Division of Molecular Medicine, Ruether Boskovae Institute, POB 180, 10002 Zagreb, Croatia.
Psychopharmacology (Berl). 2003 Jun;167(4):373-9. doi: 10.1007/s00213-002-1357-y. Epub 2003 Apr 15.
Several studies have shown that swim stress lowers the convulsant potency of different convulsants. The involvement of alpha(2)-()adrenoceptors has been proposed. Drugs active at alpha(2)-adrenoceptors are known to modulate the head twitch response, the behaviour supposedly mediated by 5-HT(2A) receptors.
We tested whether swim stress modulates head twitch behaviour in mice and whether alpha(2)-adrenoceptors interfere with this effect.
The mice were stressed (10 min swimming at 18-19 degrees C), and the head twitch response was produced by 5-hydroxytryptophan (5-HTP, the precursor of serotonin) or by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, a selective 5-HT(2) receptor agonist) administered IP before or after swimming. Yohimbine (a non-selective alpha(2)-adrenoceptor antagonist), idazoxan (a selective alpha(2)-adrenoceptor antagonist) and diazepam were also used.
Swim stress inhibited profoundly the 5-HTP-induced head twitch behaviour in mice. alpha(2)-Adrenoceptor antagonists and diazepam failed to counteract this effect. The head twitch behaviour produced by DOI given before or after stress was also inhibited. Repeatedly stressed mice had only a mild inhibition of the head twitch response.
The results demonstrate that swim stress inhibits, by an alpha(2)-adrenoceptor unrelated mechanism, 5-HT(2A) receptor-mediated head twitch behaviour in mice, suggesting that this effect and the swim stress-induced anticonvulsant effect are produced by two separate and independent mechanisms.
多项研究表明，游泳应激会降低不同惊厥剂的惊厥效力。有人提出这与α₂-肾上腺素能受体有关。已知作用于α₂-肾上腺素能受体的药物可调节头部抽搐反应，这种行为推测是由5-羟色胺（5-HT₂A）受体介导的。
我们测试了游泳应激是否会调节小鼠的头部抽搐行为，以及α₂-肾上腺素能受体是否会干扰这种效应。
对小鼠施加应激（在18-19摄氏度下游泳10分钟），在游泳前后腹腔注射5-羟色氨酸（5-HTP，血清素的前体）或1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI，一种选择性5-HT₂受体激动剂）来引发头部抽搐反应。还使用了育亨宾（一种非选择性α₂-肾上腺素能受体拮抗剂）、咪唑克生（一种选择性α₂-肾上腺素能受体拮抗剂）和地西泮。
游泳应激显著抑制了小鼠中5-HTP诱导的头部抽搐行为。α₂-肾上腺素能受体拮抗剂和地西泮未能抵消这种效应。应激前后给予DOI所产生的头部抽搐行为也受到抑制。反复应激的小鼠对头部抽搐反应仅有轻微抑制。
结果表明，游泳应激通过一种与α₂-肾上腺素能受体无关的机制抑制小鼠中5-HT₂A受体介导的头部抽搐行为，这表明这种效应和游泳应激诱导的抗惊厥效应是由两种独立且不相关的机制产生的。
