Effect of Environmental Concentration of Carbamazepine on the Behaviour and Gene Expression of Laboratory Rats

SIMPLE SUMMARY: Carbamazepine is an active compound in commonly used drugs for the treatment of epilepsy and other diseases. It is a very stable substance that remains in the environment, especially in waste water, but also in surface water. Because of this, it can pose a potential risk to both animals and humans. Although its effect in therapeutic doses has been described, the effects of low doses on the environment are unknown. We were interested in whether the consumption of food contaminated with carbamazepine can cause certain changes in behaviour and whether it simultaneously affects gene expression in higher vertebrates. The laboratory rats served as model organisms. The animals were divided into three groups, where one group orally received a high therapeutic dose of carbamazepine, the second received a low environmental dose, and the third control group received a solution without carbamazepine. The results of behavioural testing, which focused on cognitive abilities, anxiety-like behaviour, and social behaviour, did not reveal any changes; however, the expression of a certain gene on the brain of rats was affected by carbamazepine. ABSTRACT: Carbamazepine (CBZ), an effective drug for epilepsy and other neurological diseases, and its metabolites are one of the most frequently detected substances in the aquatic environment. Although these are doses of very low concentrations, chronic exposure to them can affect the physiological processes of living organisms. This experiment may clarify if carbamazepine, under an environmental and a therapeutic concentration, can affect the behaviour of higher vertebrates, especially mammals, and gene expressions of Ugt1a6 and Ugt1a7 in the brain compared to the control group without exposure to CBZ. Three groups of thirteen rats were randomly formed, and each group was treated either with carbamazepine 12 mg/kg (therapeutic), carbamazepine 0.1 mg/kg (environmental), or by 10% DMSO solution (control). The memory, anxiety, and social behaviour of the rats were assessed by the test Elevated Plus Maze, the novel object recognition test, and the social chamber paradigm. After testing, they were euthanised and brain tissue samples were collected and analysed for mRNA expression of Ugt1a6 and Ugt1a7 genes. The tests did not show significant differences in the behaviour of the rats between the groups. However, there were significant changes at the gene expression level of Ugt1a7.