Assessing the effects of 5-HT 2A and 5-HT 5A receptor antagonists on DOI-induced head-twitch response in male rats using marker-less deep learning algorithms.

Autor: Cyrano E; Behavioral Neuroscience and Drug Development, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, Kraków, 31-343, Poland., Popik P; Behavioral Neuroscience and Drug Development, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, Kraków, 31-343, Poland. nfpopik@cyf-kr.edu.pl.
Jazyk: angličtina
Zdroj: Pharmacological reports : PR [Pharmacol Rep] 2024 Nov 27. Date of Electronic Publication: 2024 Nov 27.
DOI: 10.1007/s43440-024-00679-1
Abstrakt: Background: Serotonergic psychedelics, which display a high affinity and specificity for 5-HT 2A receptors like 2,5-dimethoxy-4-iodoamphetamine (DOI), reliably induce a head-twitch response in rodents characterized by paroxysmal, high-frequency head rotations. Traditionally, this behavior is manually counted by a trained observer. Although automation could simplify and facilitate data collection, current techniques require the surgical implantation of magnetic markers into the rodent's skull or ear.
Methods: This study aimed to assess the feasibility of a marker-less workflow for detecting head-twitch responses using deep learning algorithms. High-speed videos were analyzed using the DeepLabCut neural network to track head movements, and the Simple Behavioral Analysis (SimBA) toolkit was employed to build models identifying specific head-twitch responses.
Results: In studying DOI (0.3125-2.5 mg/kg) effects, the deep learning algorithm workflow demonstrated a significant correlation with human observations. As expected, the preferential 5-HT 2A receptor antagonist ketanserin (0.625 mg/kg) attenuated DOI (1.25 mg/kg)-induced head-twitch responses. In contrast, the 5-HT 5A receptor antagonists SB 699,551 (3 and 10 mg/kg), and ASP 5736 (0.01 and 0.03 mg/kg) failed to do so.
Conclusions: Previous drug discrimination studies demonstrated that the 5-HT 5A receptor antagonists attenuated the interoceptive cue of a potent hallucinogen LSD, suggesting their anti-hallucinatory effects. Nonetheless, the present results were not surprising and support the head-twitch response as selective for 5-HT 2A and not 5-HT 5A receptor activation. We conclude that the DeepLabCut and SimBA toolkits offer a high level of objectivity and can accurately and efficiently identify compounds that induce or inhibit head-twitch responses, making them valuable tools for high-throughput research.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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