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


OBJECTIVE
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.
Pericić
Danka
D
Laboratory for Molecular Neuropharmacology, Division of Molecular Medicine, Ruether Boskovae Institute, POB 180, 10002 Zagreb, Croatia. pericic@rudjer.irb.hr
D006916:5-Hydroxytryptophan; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D019416:Head Movements / Q000187:drug effects*; D007215:Indophenol / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology*; D013550:Swimming
D058669:Adrenergic alpha-2 Receptor Antagonists; D000927:Anticonvulsants; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; C113896:dimethoxy-4-indophenyl-2-aminopropane; D007215:Indophenol; D006916:5-Hydroxytryptophan; D003975:Diazepam