Ceftriaxone Inhibits Conditioned Fear and Compulsive-like Repetitive Marble Digging without Central Nervous System Side Effects Typical of Diazepam—A Study on DBA2/J Mice and a High-5HT Subline of Wistar–Zagreb 5HT Rats

Poljak, Ljiljana; Miše, Branko; Čičin-Šain, Lipa; Tvrdeić, Ante (2024) Ceftriaxone Inhibits Conditioned Fear and Compulsive-like Repetitive Marble Digging without Central Nervous System Side Effects Typical of Diazepam—A Study on DBA2/J Mice and a High-5HT Subline of Wistar–Zagreb 5HT Rats. Biomedicines, 12 (8). ISSN 2227-9059

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Abstract

Ceftriaxone upregulates GLT1 glutamate transporter in the brain and may have anti-CFC and anti-OCD effects. Methods: Twenty WZ-5HT rats were used to investigate the effects of ceftriaxone on obsessive–compulsive (OCD)-like behaviour in the marble-burying (MB) test, freezing behaviour in contextual fear conditioning (CFC) and expression of GLT1 protein in the hippocampus or amygdala using immunoblots. Fifteen DBA/2J mice were used in the MB test. We also compared diazepam with ceftriaxone in open-field, beam-walking, and wire-hanging tests on 47 DBA/2J mice. Ceftriaxone (200 mg/kg) and saline were applied intraperitoneally, once daily for 7 (rats) or 5 (mice) consecutive days. A single dose of diazepam (1.5–3.0 mg/kg) or saline was injected 30 min before the behavioural tests. Results: Ceftriaxone significantly diminished OCD-like behaviour (↓ number of marbles buried) and freezing behaviour in CFC context session (↑ latencies, ↓ total duration, ↓ duration over four 2 min periods of the session) but increased GLT1 protein expression in the amygdala and hippocampus of rats. Diazepam induced sedation, ataxia and myorelaxation in mice. Ceftriaxone did not have these side effects. Conclusions: The results of this study confirm the anti-CFC and anti-OCD effects of ceftriaxone, which did not produce the unwanted effects typical of diazepam.

Item Type:	Article
Uncontrolled Keywords:	ceftriaxone; GLT1/EAAT2 transporter; WZ-5HT rats; marble-burying test; contextual fear conditioning; OCD; PTSD; amygdala and hippocampus
Subjects:	BIOMEDICINE AND HEALTHCARE
Divisions:	Division of Molecular Biology
Depositing User:	Ivana Vuglec
Date Deposited:	13 Oct 2025 08:31
URI:	http://fulir.irb.hr/id/eprint/9988
DOI:	10.3390/biomedicines12081711

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