Keywords

Huntington Disease; Psychoplastogen; Depression; Neurodegenerative; Psychedelic; Apathy

Abstract

Huntington Disease (HD) is a neurodegenerative disorder caused by an expansion in the trinucleotide CAG repeat on exon 1 of the huntingtin gene. In HD one of the first symptoms is often depression. In cases where SSRIs fail, treatments for treatment-resistant depression often become a patient’s only option. These rigorous treatments, such as electroconvulsive therapy, are not suitable for this patient population as it can worsen motor symptoms. In order to search for potential alternatives, we queried whether depressive-like behavior could be reduced in Hu97/18 and Q175FDN HD mice by administering tabernanthalog, a non-hallucinogenic psychedelic analog. Our study is not completed at this time as not all cohorts have reached the age of testing. In our preliminary studies reported here, we have found that compared to Hu18/18 control littermates, Hu97/18 mice do not display apathy as assessed by the sucrose splash test, however, tabernanthalog treatment did decrease apathy-like behavior in female Hu97/18 mice. We did not observe a significant effect of tabernanthalog treatment on depressive-like behavior during the forced swim test, but there was a trend towards an anti-depressant-like effect. Further testing is ongoing to include the rest of the Hu97/18 mice in this trial, followed by repeating the same trial in the Q175FDN mice. Our future findings could potentially provide proof of principle for the use of psychoplastogens for treatment-resistant depression in HD.

Thesis Completion Year

2025

Thesis Completion Semester

Spring

Thesis Chair

Southwell, Amber

College

College of Medicine

Department

Neuroscience

Thesis Discipline

Biomedical Sciences

Language

English

Access Status

Open Access

Length of Campus Access

None

Campus Location

Orlando (Main) Campus

Subjects

Huntington's disease--Research; Huntington's disease--Animal models; Depression, Mental--Research; Psychopharmacology--Research; Neuropsychopharmacology--Research

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