S-104 | EFFECTS OF IBOGAINE ON HIPPOCAMPAL CA1 LONG-TERM PLASTICITY IN MICE LACKING 5HT2A RECEPTORS

S-104 | EFFECTS OF IBOGAINE ON HIPPOCAMPAL CA1 LONG-TERM PLASTICITY IN MICE LACKING 5HT2A RECEPTORS 150 150 SAN 2024 Annual Meeting

Neural excitability, synaptic transmission and neuron-glia interactions
Author: Natasha Maria Brun | Email: natbrun17@gmail.com


Natasha M. Brun, Sofía Villalba1°2°, Afsaneh Labbaf,  Pablo Torterolo, Ignacio Carrera, Verónica Bisagno, Francisco J. Urbano

IFIBYNE-CONICET, Buenos Aires, Argentina
Austral Univ., Derqui, Pilar., Argentina
School of Medicine, Univ. de la República, Montevideo, Uruguay
School of Chemistry, Univ. de la República, Montevideo, Uruguay

NMDA receptor–dependent long-term potentiation (LTP) in hippocampal CA3-CA1 Schaffer collateral synapses has been extensively studied in vitro. Ibogaine, the main indole alkaloid isolated from the root bark of the African shrub Tabernanthe iboga, is an atypical psychedelic drug capable of inducing oneirogenic effects and vivid memory recall, as well as antiaddictive and antidepressive effects. Ibogaine is known to block open NMDA receptors in a use-and voltage-dependent manner during whole-cell recording in cell cultures. The main objective of this study was to analyze the effect of ibogaine (50 microM) in vitro field potentials recorded at CA1 stratum radiatum (apical dendrites) of hippocampal 300 microM thick coronal slices from 5-HT2A receptor knockout (KO) (5-HT2A -/-) or wild type (WT) male mice. We induced LTP using a strong tetanus (5x 100 ms long 100 Hz trains) of the Schaffer´s collaterals using a bipolar electrode. Tetanic stimulation was applied after 20-30 minute baseline recording in presence of bicuculline (10 microM, GABA-A receptor inhibitor) or bicuculline+ibogaine (50 microM). Results show an enhancement of baseline glutamate release after 20 min ibogaine application in WT slices but not 5-HT2A KO mice (One-way RM ANOVA). A statistically significant postetanic response was observed from both WT and 5-HT2A KO slices (One-way RM ANOVA). Results suggest that in vitro ibogaine hippocampal synaptic effects involve 5-HT2A receptors dependent pathways.

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