INTRODUCTION: Major depressive disorder (MDD) is one of the main causes of disability worldwide, with approximately 30% of patients failing to respond to standard treatment methods, such as selective serotonin reuptake inhibitors (SSRI). The term treatment-resistant depression (TRD) was coined to describe depressive symptoms that fail to improve after at least two courses of adequate treatment. Although knowledge about this disorder is limited, there are animal models that are used to study its etiology. Wistar Kyoto rats display a stress-prone and depression-like phenotype, although little is known about its underlying morphological and neurochemical substrates, especially in the dorsal raphe (DRN) - the main serotoninergic (5-HT) nucleus in the brain. This animal model responds to ketamine, but not SSRI treatment, which might indicate altered serotonin system function and/or morphology.

AIM(S): We aimed to morphologically and electrophysiologically characterize 5-HT DRN neurons in Wistar and Wistar Kyoto rats to gain insight about the state of the serotonin system in the TRD model.

METHOD(S): We performed whole-cell patch clamp recordings of intrinsic passive and active membrane properties, as well as excitatory and inhibitory transmission in the DRN. All cells were filled with biocytin during recording and slices were later immunostained for tyrosine- and tryptophan hydroxylase, as markers of dopaminergic and serotonergic neurons respectively.

RESULTS: Preliminary recordings have revealed a heterogenous distribution of morphological and electrophysiological features of 5-HT DRN neurons in both strains. Moreover, these characteristics correlate to anatomical subdivisions within the broad DRN hub.

CONCLUSIONS: As 5-HT remains one of the main neuromodulators involved in mood regulation, the differences we observed might contribute towards understanding the distinct neural substrates of the behavioral characteristics and treatment-resistant phenotype observed in Wistar Kyoto rats.

FINANCIAL SUPPORT: Grant NCN OPUS 25 nr.: 2023/49/B/NZ4/03592 ID: 591148