Long-Term Propranolol Treatment Induces Anxiolytic-like Effects and Alters Hypothalamic Noradrenergic, Serotonergic and GABAergic Neurotransmission
4 affiliations
- 1Department of Organic Chemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland
- 2Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, Banacha 1b, 02-097 Warsaw, Poland
- 3Central Laboratory of Laboratory Animals, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Banacha 1b, 02-097 Warsaw, Poland
- 4Faculty of Chemistry, Nicolaus Copernicus University, 7 Gagarina St., 87-100 Toruń, Poland
Abstract
Propranolol is a non-selective β-adrenergic receptor antagonist widely used in cardiovascular medicine and anxiety-related conditions; however, its central neurochemical mechanisms remain incompletely understood. This study investigated the effects of long-term propranolol administration on anxiety-like behavior and hypothalamic neurotransmission in rats. Adult male Sprague–Dawley rats received propranolol in drinking water at doses of 1, 2.5, or 5 mg/kg b.w./day for 33 days. Behavioral effects were assessed using the Open Field Test (OF) and Elevated Plus Maze (EPM). Hypothalamic concentrations of amino acids, e.g., γ-aminobutyric acid (GABA) as well as monoamines, and their metabolites were determined by high-performance liquid chromatography with electrochemical detection (HPLC-ED). Long-term propranolol treatment induced a significant anxiolytic-like effect, reflected by increased exploration of open arms in the EPM, without affecting locomotor activity in the OF. Neurochemical analyses revealed a significant increase in hypothalamic GABA levels and a marked reduction in noradrenergic turnover, as indicated by decreased MHPG/NA ratios. Propranolol also increased hypothalamic serotonin concentrations, whereas dopaminergic turnover remained unchanged. These findings demonstrate that long-term propranolol administration produces neurochemical changes within the hypothalamus involving noradrenergic, serotonergic, and GABAergic signaling pathways. The results suggest that the anxiolytic-like effects of propranolol extend beyond β-adrenergic receptor blockade and may be mediated by coordinated modulation of multiple neurotransmitter systems involved in stress regulation and emotional processing. The study provides new evidence linking chronic propranolol exposure to selective hypothalamic neurochemical remodeling associated with reduced anxiety-like behavior.
Related
BibTeX
@article{witczynska2026longterm,
title = {{Long-Term Propranolol Treatment Induces Anxiolytic-like Effects and Alters Hypothalamic Noradrenergic, Serotonergic and GABAergic Neurotransmission}},
author = {Adrianna Witczyńska and Łukasz Fijałkowski and Kamilla Blecharz-Klin and Katarzyna Ziętal and Justyna Pyrzanowska and Agnieszka Piechal and Ilona Joniec-Maciejak and Ewa Machaj and Agnieszka Jastrzębska and Jacek Nowaczyk and Dagmara Mirowska-Guzel and Alicja Nowaczyk},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219755},
url = {https://www.mdpi.com/1422-0067/27/21/9755},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Long-Term Propranolol Treatment Induces Anxiolytic-like Effects and Alters Hypothalamic Noradrenergic, Serotonergic and GABAergic Neurotransmission
AU - Adrianna Witczyńska
AU - Łukasz Fijałkowski
AU - Kamilla Blecharz-Klin
AU - Katarzyna Ziętal
AU - Justyna Pyrzanowska
AU - Agnieszka Piechal
AU - Ilona Joniec-Maciejak
AU - Ewa Machaj
AU - Agnieszka Jastrzębska
AU - Jacek Nowaczyk
AU - Dagmara Mirowska-Guzel
AU - Alicja Nowaczyk
PY - 2026
DA - 2026/10/30
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219755
UR - https://www.mdpi.com/1422-0067/27/21/9755
AB - Propranolol is a non-selective β-adrenergic receptor antagonist widely used in cardiovascular medicine and anxiety-related conditions; however, its central neurochemical mechanisms remain incompletely understood. This study investigated the effects of long-term propranolol administration on anxiety-like behavior and hypothalamic neurotransmission in rats. Adult male Sprague–Dawley rats received propranolol in drinking water at doses of 1, 2.5, or 5 mg/kg b.w./day for 33 days. Behavioral effects were assessed using the Open Field Test (OF) and Elevated Plus Maze (EPM). Hypothalamic concentrations of amino acids, e.g., γ-aminobutyric acid (GABA) as well as monoamines, and their metabolites were determined by high-performance liquid chromatography with electrochemical detection (HPLC-ED). Long-term propranolol treatment induced a significant anxiolytic-like effect, reflected by increased exploration of open arms in the EPM, without affecting locomotor activity in the OF. Neurochemical analyses revealed a significant increase in hypothalamic GABA levels and a marked reduction in noradrenergic turnover, as indicated by decreased MHPG/NA ratios. Propranolol also increased hypothalamic serotonin concentrations, whereas dopaminergic turnover remained unchanged. These findings demonstrate that long-term propranolol administration produces neurochemical changes within the hypothalamus involving noradrenergic, serotonergic, and GABAergic signaling pathways. The results suggest that the anxiolytic-like effects of propranolol extend beyond β-adrenergic receptor blockade and may be mediated by coordinated modulation of multiple neurotransmitter systems involved in stress regulation and emotional processing. The study provides new evidence linking chronic propranolol exposure to selective hypothalamic neurochemical remodeling associated with reduced anxiety-like behavior.
SN - 1422-0067
ER -