Swim stress inhibits 5-HT2A receptor-mediated head twitch behaviour in mice

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.