Modulation of certain 5-HT-related behaviours by serotonergic and noradrenergic systems
The modulation of 5-hydroxytryptamine (5-HT)-related head-twitch behaviour by antimigraine drugs and migraine triggers were examined in mice. In general, antimigraine drugs were found to inhibit 5-HT-related head-twitching. The migraine triggers examined, tyramine and beta-PEA produced a complex time-related effect on 5-HT-related head-twitching, with both inhibition and potentiation of this behaviour being observed. It is suggested that the 5-HT-related head-twitch may be useful in examining the pharmacology of migraine, and possibly, in the preclinical screening and discovery of systemically-active antimigraine agents. The effect of ()-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, (()DOI), on on-going behaviour of mice and rats was examined. Shaking behaviour was observed in both species. In mice, excessive scratching behaviour was also present. ()DOI-induced scratching and shaking behaviour were found to be differentially modulated by noradrenergic and serotonergic agents, however, the fact that both behaviours were blocked by ritanserin (5-HT2/5-HT1c receptor antagonist) and inhibited by FLA-63 (a dopamine-beta-oxidase inhibitor which depletes noradrenaline), suggests the pathways mediating these behaviours must be convergent in some manner, and that both behaviours require intact 5-HT receptors, probably 5-HT2 receptors, for their production. In general, the behavioural profile of ()DOI was as expected for an agent which exhibits high affinity binding to 5-HT2/5-HT1c receptors. Little sign of the 5-HT1-related `5-HT syndrome' was seen in either mice or rats. The effect of a variety of noradrenergic agents on head-twitching induced by a variety of shake-inducing agents was examined. A pattern of modulatory effect was seen whereby the modulatory effect of the noradrenergic agents on 5-hydroxytryptophan (5-HTP) (and in some cases, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)) was found to be the opposite of that observed with quipazine and ()DOI.