Peptide Modulator of TRPV1 Channel Increases Long-Term Potentiation in the Hippocampus and Reduces Anxiety and Fear in Mice Under Acute Stress

Pavlov, Vladimir M.; Fedotova, Anastasia Yu.; Palikov, Victor A.; Logashina, Yulia A.; Zagitova, Kamilla I.; Dyachenko, Igor A.; Popov, Alexander V.; Andreev, Yaroslav A.

doi:10.3390/md24020059

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Peptide Modulator of TRPV1 Channel Increases Long-Term Potentiation in the Hippocampus and Reduces Anxiety and Fear in Mice Under Acute Stress

by

Vladimir M. Pavlov

^1,2

,

Anastasia Yu. Fedotova

^1,2,

Victor A. Palikov

^1,2

,

Yulia A. Logashina

³,

Kamilla I. Zagitova

³,

Igor A. Dyachenko

^1,2

,

Alexander V. Popov

^3,4 and

Yaroslav A. Andreev

^3,*

¹

Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki Avenue, 142290 Pushchino, Moscow region, Russia

²

Pushchino Branch of the Federal State Budgetary Educational Institution of Higher Education “Russian Biotechnological University (BIOTECH University)”, Prospekt Nauki, 3, 142290 Pushchino, Moscow region, Russia

³

Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia

⁴

Kurchatov Medical Primatology Center of National Research Center «Kurchatov Institute», 354376 Sochi, Russia

^*

Author to whom correspondence should be addressed.

Mar. Drugs 2026, 24(2), 59; https://doi.org/10.3390/md24020059 (registering DOI)

Submission received: 27 November 2025 / Revised: 14 January 2026 / Accepted: 27 January 2026 / Published: 31 January 2026

(This article belongs to the Section Marine Pharmacology)

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Abstract

One of the attractive targets for the relief of stress conditions is TRPV1, which is expressed mostly in primary afferent neurons (nociceptors) and in the central nervous system, mainly in the cortex and hippocampus. We evaluated the action of a potent low-molecular-weight antagonist of TRPV1 (AMG517) and peptide modulator of this channel (APHC3) on long-term potentiation (LTP) and Paired-Pulse Ratio (PPR) in the CA3-CA1 region of the hippocampus of mice. In vivo, we used intranasal administration to provide effective peptide delivery into the brain and analyzed the effects of APHC3 in acute stress tests in comparison with intramuscular administration of APHC3, AMG517, and the reference anxiolytic drug Fabomotizole (Fab). In electrophysiology studies, APHC3 significantly enhanced LTP and PPR, while AMG517 enhanced only PPR. Intranasal administration of APHC3 to mice provided a moderate anxiolytic effect in the single dose (0.01 mg/kg). Intramuscular administration of APHC3 and AMG517 significantly reduced acute stress in mice equal to the reference drug Fab. Thus, TRPV1 modulation in either the peripheral or central nervous system is sufficient to produce an anxiolytic-like effect, likely through distinct underlying mechanisms.

Keywords: TRPV1; sea anemone peptide; toxin; long-term potentiation (LTP); paired-pulse ratio (PPR); anxiolytic effect; anxiety; fear

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MDPI and ACS Style

Pavlov, V.M.; Fedotova, A.Y.; Palikov, V.A.; Logashina, Y.A.; Zagitova, K.I.; Dyachenko, I.A.; Popov, A.V.; Andreev, Y.A. Peptide Modulator of TRPV1 Channel Increases Long-Term Potentiation in the Hippocampus and Reduces Anxiety and Fear in Mice Under Acute Stress. Mar. Drugs 2026, 24, 59. https://doi.org/10.3390/md24020059

AMA Style

Pavlov VM, Fedotova AY, Palikov VA, Logashina YA, Zagitova KI, Dyachenko IA, Popov AV, Andreev YA. Peptide Modulator of TRPV1 Channel Increases Long-Term Potentiation in the Hippocampus and Reduces Anxiety and Fear in Mice Under Acute Stress. Marine Drugs. 2026; 24(2):59. https://doi.org/10.3390/md24020059

Chicago/Turabian Style

Pavlov, Vladimir M., Anastasia Yu. Fedotova, Victor A. Palikov, Yulia A. Logashina, Kamilla I. Zagitova, Igor A. Dyachenko, Alexander V. Popov, and Yaroslav A. Andreev. 2026. "Peptide Modulator of TRPV1 Channel Increases Long-Term Potentiation in the Hippocampus and Reduces Anxiety and Fear in Mice Under Acute Stress" Marine Drugs 24, no. 2: 59. https://doi.org/10.3390/md24020059

APA Style

Pavlov, V. M., Fedotova, A. Y., Palikov, V. A., Logashina, Y. A., Zagitova, K. I., Dyachenko, I. A., Popov, A. V., & Andreev, Y. A. (2026). Peptide Modulator of TRPV1 Channel Increases Long-Term Potentiation in the Hippocampus and Reduces Anxiety and Fear in Mice Under Acute Stress. Marine Drugs, 24(2), 59. https://doi.org/10.3390/md24020059

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Peptide Modulator of TRPV1 Channel Increases Long-Term Potentiation in the Hippocampus and Reduces Anxiety and Fear in Mice Under Acute Stress

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