The effect of 3-di-o-tolylguanidine on the level of neurotransmitters in the cerebellum and related disorders of social behavior

• Published in: Neuroscience 2024-12, Vol.565, p.549-557
• Main Authors: Piechal, Agnieszka, Blecharz-Klin, Kamilla, Jakimiuk, Alicja, Pyrzanowska, Justyna, Joniec-Maciejak, Ilona, Mirowska-Guzel, Dagmara, Widy-Tyszkiewicz, Ewa
• Format: Article
• Language: English
• Subjects: Cerebellum; Neurotransmitters; Social behavior; Tolylguanidine
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2024.12.017

[Display omitted] •5-di-o-tolylguanidine disrupts social behavior in rats.•5-di-o-tolylguanidine has an effect on dopaminergic and serotonergic neurotransmission in cerebellum.•5-di-o-tolylguanidine affects concentration of certain amino acids in cerebellum. It is common knowledge that the cerebellum is a structure of the central nervous system that influences the processes of balance and motor coordination. Recently its influence on social interactions has also been emphasized. The sigma receptor agonist: 3-di-o-tolylguanidine (DTG) is characterized by high affinity for sigma 1 and sigma 2 receptors, widely distributed in the cerebellum. In the experiment we assessed the effect of long term administration of DTG to adult male Sprague Dawley rats on social behavior and the concentration of neurotransmitters in the cerebellum. DTG was administered orally at a dose of 3 mg/kg body weight (bw) (DTG3), 10 mg/kg bw (DTG10) and 30 mg/kg bw (DTG30) for 9 weeks before the behavioral test. After the experiment, the concentration of catecholamines and amino acids in the cerebellum was assessed using high performance liquid chromatography (HPLC). Treatment groups showed reductions in social interactions such as grooming, sniffing and total time spent interacting. At the same time, it was shown that in the group receiving the lowest dose of the drug, a decrease in the concentration of dopamine and serotonin in the cerebellum was observed. Furthermore, changes in the concentration of taurine, alanine, glutamic acid and gamma-aminobutyric acid were observed in the treated groups. We found that long term administration of DTG disturbs animals’ social interactions and the concentration of neurotransmitters in the cerebellum.