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Journal of Psychopharmacology
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Effects of idazoxan on 5-hydroxytryptamine-mediated behaviour in the mouse and rat

S.L. Dickinson

Reckitt and Colman Psychopharmacology Unit, The School of Medical Sciences, University Walk, Bristol BS8 1TD

I.F. Tulloch

Reckitt and Colman Pharmaceuticals, Dansom Lane, Kingston-Upon-Hull HU8 7DS, UK

B. Gadie

Reckitt and Colman Pharmaceuticals, Dansom Lane, Kingston-Upon-Hull HU8 7DS, UK

The {alpha}2-adrenoceptor antagonists idazoxan and RX811059 induced reciprocal forepaw treading, a component of the 5-HT-behavioural syndrome in rats. This response is independent of 'non-{alpha}2-adrenoceptor idazoxan binding sites' (NAIBS) at which RX811059 is inactive. Idazoxan pre-treatment, in rats, enhanced forepaw treading, head weaving and tremor induced by the 5-HT agonist 5-methoxy-N,N dimethyltryptamine (5-MeODMT), increased head twitches (but decreased hindlimb abduction) induced by the 5-HT releaser p- chloroamphetamine (pCA), but did not clearly alter head twitches induced by the 5-HT precursor L-5-hydroxytryptophan in mice. The {alpha}1-antagonist prazosin did not alter behaviour induced by either 5-MeODMT or pCA in rats. The {alpha} 2-agonist, guanoxabenz, did not alter 5-MeODMT-induced behaviour in rats. St587, an {alpha}1-agonist, selectively potentiated tremor induced by 5-MeODMT, but no other behaviour. A possible mechanism for these interactions could be through enhanced, {alpha}2-adrenoceptor-mediated, 5-HT release in specific brain areas. Other possibilities, e.g. direct action at subtypes of 5-HT receptors and the importance of these NA-5-HT interactions in the treatment of resistant depression, are discussed.

Journal of Psychopharmacology, Vol. 5, No. 3, 187-195 (1991)
DOI: 10.1177/026988119100500302
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