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Possible mechanism of 5-methoxy-N,N-dimethyltryptamine-induced turning behaviour in DRN lesioned rats.

T P Blackburn, B Cox, C G Heapy, T F Lee

Pharmacology, biochemistry, and behavior January 1, 1982 DOI: 10.1016/0091-3057(82)90004-1 via PubMed

Summary

AI-generated from the abstract

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.

Study at a glance

Characteristics Experimental study Peer reviewed
Population Rats with unilateral dorsal raphe nucleus lesions
Interventions 5-MeODMT methysergide cyproheptadine cinanserin xylamidine haloperidol hyoscine picrotoxin naloxone strychnine alpha-methyl-p-tyrosine 6-hydroxydopamine
Dose 7.5 mg/kg SC
Citations 4
Key finding 5-MeODMT-induced contralateral turning in DRN-lesioned rats involves a central dopaminergic system.

Abstract

5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) (7.5 mg/kg SC) caused a contralateral turning in rats with a unilateral lesion of the dorsal raphe nucleus (DRN). This turning behaviour was blocked by pretreatment with putative 5-HT antagonists, methysergide, cyproheptadine and cinanserin. The peripheral 5-HT antagonist, xylamidine, also prevented the response to 5-MeODMT. Of the other neurotransmitter antagonists, only haloperidol was active, hyoscine, picrotoxin, naloxone and strychnine were ineffective. Pretreatment with alpha-methyl-p-tyrosine (alpha-MT) also significantly reduced the turning response to 5-MeODMT. These results indicate that a central dopaminergic system is involved in 5-MeODMT-induced turning behaviour. This suggestion is supported by the finding that an ipsilateral turning in response to 5-MeODMT was observed in the rats with additional 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle (MFB). The possible mechanisms by which 5-MeODMT induced turning in DRN lesioned rats are discussed.

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