Increased Density of D2-like, but Not D1-like, Dopamine Receptors in the Caudal Dorsal Striatum of Rats with Different Forms of Generalized Epilepsy

The striatal dopaminergic system plays an important role in modulating seizure activity; however, regional differences in the distribution of D1- and D2-like receptors (D1R/D2R) in various forms of epilepsy remain insufficiently studied. In this work, autoradiography was used to investigate the binding density of [3H]SCH23390 (D1R) and [3H]spiperone (D2R) in the caudal regions of the dorsal striatum in rats with genetic generalized epilepsies: audiogenic (KM strain), absence (WAG/Rij), and mixed (WAG/Rij-AGS), as well as in control Wistar rats. It was shown that all studied epilepsy models exhibited a significant increase in D2R density in the caudal striatum, and its dorsolateral subregions (areas receiving projections from the dorsolateral part of the substantia nigra), while D1R density remained unchanged. The most pronounced changes were observed in KM rats with audiogenic epilepsy, which may reflect striatal compensatory mechanisms to hyperexcitability of brainstem structures. The obtained data expand our understanding of the neurochemical basis of epileptogenesis and highlight the potential significance of the caudal striatum as a therapeutic target for convulsive epilepsies and epilepsy-associated comorbidities.