Involvement of a central dopaminergic system in 5-methoxy-N,N-dimethyltryptamine-induced turning behaviour in rats with lesions of the dorsal raphé nuclei.
Psychopharmacology January 1, 1982 DOI: 10.1007/BF00428162 via PubMed
Summary
AI-generated from the abstractIn rats with lesions of the dorsal raphé nucleus, the compound 5-MeODMT caused contralateral turning, similar to its effect in rats with substantia nigra lesions. Ipsilateral turning occurred when 5-MeODMT was given to rats with striatal lesions. The turning behavior in dorsal raphé-lesioned rats was reduced by a second lesion in the striatum but not in the nucleus accumbens, implicating the nigrostriatal dopaminergic system. In substantia nigra slices, 5-MeODMT inhibited dopamine release, an effect blocked by methysergide but not tetrodotoxin, suggesting 5-MeODMT reduces dopamine release from nigral dendrites, enhancing nigrostriatal activity and causing contralateral turning.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats with lesions of the dorsal raphé nucleus, substantia nigra, or striatum |
| Interventions | 5-MeODMT 5 7-DHT lesions methysergide tetrodotoxin |
| Dose | 10^-7 to 10^-5 M |
| Citations | 6 |
| Key finding | 5-MeODMT induces contralateral turning in dorsal raphé-lesioned rats via inhibition of dopamine release from nigral dendrites, mediated by the nigrostriatal dopaminergic system. |
Abstract
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.