In 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.
In rats with a unilateral lesion of the dorsal raphe nucleus (DRN), the compound 5-MeODMT caused turning toward the opposite side. This behavior was blocked by several serotonin antagonists, including methysergide, cyproheptadine, cinanserin, and the peripheral antagonist xylamidine. Among other neurotransmitter antagonists tested, only haloperidol was effective; hyoscine, picrotoxin, naloxone, and strychnine were not. Pretreatment with alpha-methyl-p-tyrosine also reduced the turning. These results suggest involvement of a central dopaminergic system. Additional lesions of the medial forebrain bundle with 6-OHDA changed the turning direction to the same side, supporting this interpretation.