Involvement of a central dopaminergic system in 5-methoxy-N,N-dimethyltryptamine-induced turning behaviour in rats with lesions of the dorsal raphé nuclei.
The turning behaviour induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) has been investigated in rats with lesions of the dorsal raphé nucleus (DRN). 5-MeODMT caused a dose-related contralateral turning in rats with 5,7-dihydroxytryptamine (5,7-DHT) lesions of the substantia nigra and a similar effect was observed in DRN-lesioned rats. In contrast, a dose-related ipsilateral turning was observed when 5-MeODMT was injected into rats with 5,7-DHT lesions of the striatum. These results suggest that the effects of 5-MeODMT in DRN-Lesioned rats are mediated via the substantia nigra. The contralateral turning induced by 5-MeODMT in rats with a 5,7-DHT lesion of the DRN was significantly reduced when a second 5-hydroxydopamine lesion was placed in the striatum, but not when it was placed in the nucleus accumbens. Thus the nigrostriatal dopaminergic system seems to be involved in 5-MeODMT-induced turning. The release of tritium from slices of substantia nigra previously labelled with [3H]-dopamine was inhibited by 5-MeODMT (10(-7) to 10(-5) M) and this effect was blocked by methysergide in a concentration-related manner. Tetrodotoxin (10(-7) M) failed to antagonise 5-MeODMT. These results suggest that 5-MeODMT can inhibit dopamine release from nigral dendrites, which could in turn enhance nigrostriatal activity by reducing the auto-inhibitory actions of dopamine, thereby causing contralateral turning in DRN-lesioned rats.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects; D004292:Dominance, Cerebral / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004525:Efferent Pathways / Q000187:drug effects; D006801:Humans; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology*; D009115:Muridae; D016627:Oxidopamine; D011903:Raphe Nuclei / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives* / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects
D006892:Hydroxydopamines; D008732:Methoxydimethyltryptamines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D016627:Oxidopamine; D004298:Dopamine