Danka Pericić1. 1. Laboratory for Molecular Neuropharmacology, Division of Molecular Medicine, Ruether Boskovae Institute, POB 180, 10002 Zagreb, Croatia. pericic@rudjer.irb.hr
Abstract
RATIONALE: 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. OBJECTIVES: We tested whether swim stress modulates head twitch behaviour in mice and whether alpha(2)-adrenoceptors interfere with this effect. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
RATIONALE: 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. OBJECTIVES: We tested whether swim stress modulates head twitch behaviour in mice and whether alpha(2)-adrenoceptors interfere with this effect. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: I S Chee; S W Lee; J L Kim; S K Wang; Y O Shin; S C Shin; Y H Lee; H M Hwang; M R Lim Journal: Psychiatr Genet Date: 2001-09 Impact factor: 2.458