id_729. THE EFFECT OF PSILOCIN ON NEUROTRANSMITTERS RELEASE IN THE CLAUSTRUM AND ON RAT BEHAVIOR
Zuzanna Kościuk1,2, Izabela Szpręgiel1, Agnieszka Bysiek1, Krystyna Gołembiowska1
1 Maj Institute of Pharmacology, Department of Pharmacology and Brain Biostructure, Unit II, Polish Academy of Sciences, Smętna 12, 31-343, Krakow, Poland
2 Institute of Zoology and Biomedical Research, Department of Biology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland
INTRODUCTION: The claustrum is a subcortical structure densely expressing 5-hydroxytryptamine 2A receptors (5-HT2AR). Despite its hypothesized involvement in the effects of serotonergic psychedelics, the neurochemical impact of these substances on claustral neurotransmission remains unexplored.
AIM(S): This study aimed to investigate how psilocin — a tryptamine and the active metabolite of psilocybin — and 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) — a phenethylamine and new psychoactive substance — modulate extracellular neurotransmitter levels in the rat claustrum, as well as to examine their effects on wet dog shake behavior, a proxy for hallucinogenic activity.
METHOD(S): Microdialysis probes were stereotaxically implanted into the adult male Wistar Han rats' claustrum. Rats received local administration of either psilocin (100 or 500 µM) or 25I-NBOMe (500 µM) through the microdialysis probe. Dialysate samples were collected and analyzed using high-performance liquid chromatography (HPLC) with electrochemical detection to quantify extracellular levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT), glutamate (GLU), γ-aminobutyric acid (GABA), and acetylcholine (ACh). A behavioral test defined as wet dog shakes (WDS) was conducted after drugs administration.
RESULTS: The obtained data revealed that both substances markedly altered extracellular levels of DA, 5-HT, GLU, GABA, and ACh. Psilocin significantly elevated also NA levels and produced the most pronounced enhancement of ACh signaling. 25I-NBOMe induced the greatest increase in 5-HT levels. Overall, psilocin generated a comparatively balanced excitatory–inhibitory neurochemical profile, reflecting its combined engagement of 5-HT2AR and 5-HT1AR, whereas 25I-NBOMe produced an excitation-biased pattern consistent with its selective, high-affinity 5-HT2AR agonism.
CONCLUSIONS: The observed complex neurotransmitter dynamics underscore the claustrum’s role as an integrative hub, critical for mediating the effects of psychedelic compounds.
FINANCIAL SUPPORT: This research was funded by National Science Centre grant no. 2020/37/B/NZ7/03753 and statutory funds of the Maj Institute of Pharmacology, Polish Academy of Sciences.